Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-8kt4b Total loading time: 0 Render date: 2024-07-05T01:29:23.484Z Has data issue: false hasContentIssue false

2 - Prostate cancer stem cells

from SECTION I - CHARACTERIZATION OF CANCER STEM CELLS

Published online by Cambridge University Press:  15 December 2009

By
Collene R. Jeter  and
Dean G. Tang
Edited by
William L. Farrar
Dean G. Tang
Affiliation:
University of Texas M. D. Anderson Cancer Center
Get access

Summary

STEM CELLS, PROGENITOR CELLS, AND DIFFERENTIATED CELLS

Functional regeneration, the ability of cells to reconstitute the tissue of origin, is an essential biological property of many epithelia. This unique ability suggests the presence of a renewing cell type and reflects the homeostatic mechanism that normally replaces senescent cells or cells lost to tissue damage. Not all cells within a population are equally capable of reconstitution, and this activity has been attributed to the presence of a subset of tissue-specific stem and/or progenitor cells within various epithelia, including the breast, skin, intestine, and, of particular interest, the prostate.

Cellular hierarchy is essential to the biology of complex multicellular organisms, and aberrant cell fate determination may result in pathological phenotypes. During embryogenesis, a phenomenal array of specialized cells arises from primitive, undifferentiated stem cells (SCs). The rapidly dividing cells of the early blastocyst inner-cell mass, and their derived cultured counterparts, termed embryonic stem cells (ESCs), exhibit pluripotency and unlimited proliferative potential. Both extrinsic signals and intrinsic properties converge to activate precise differentiation programs, thereby generating the phenotypically and functionally distinct lineage-restricted daughter cells present in the developing fetus.

Growth and maturation require the continual activity of stem-like cells after birth. These somatic SCs also function to repair tissue damage and maintain tissue homeostasis over time. All SCs possess remarkable proliferative potential; however, unlike ESCs, somatic SCs rarely divide. Somatic SC division is constrained by interactions within a specialized stromal cell and extracellular matrix–rich environment (the SC niche).

Type
Chapter
Information
Cancer Stem Cells , pp. 15 - 30
Publisher: Cambridge University Press
Print publication year: 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Welm, B.E., Tepera, S.B., Venezia, T., Graubert, T.A., Rosen, J.M., and Goodell, M.A. (2002) Sca-1pos cells in the mouse mammary gland represent an enriched progenitor cell population. Dev. Biol. 245, 42–56.CrossRefGoogle Scholar
Dontu, G., Abdullah, W.M., Foley, J.M., Jackson, K.W., Clarke, M.F., Kawamura, M.J., and Wicha, M. (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17, 1253–1270.CrossRefGoogle ScholarPubMed
Clarke, R.B., Spence, K., Anderson, E., Howell, A., Okano, H., and Potten, C.S. (2005) A putative human breast stem cell population is enriched for steroid receptor-positive cells. Dev. Biol. 277, 443–456.CrossRefGoogle ScholarPubMed
Shackleton, M., Vaillant, F., Simpson, K.J., Stingl, J., Smyth, G.K., Asselin-Labat, M., Wu, L., Lindeman, G.J., and Visvader, J.E. (2006) Generation of a functional mammary gland from a single stem cell. Nature 439, 84–88.CrossRefGoogle ScholarPubMed
Cotsarelis, G., Sun, T.T., and Lavker, R.M. (1990) Label-retaining cells reside in the bulge of the pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61, 1329–1337.CrossRefGoogle ScholarPubMed
Morris, R.J., Liu, Y., Marles, L., Yang, Z., Trempus, C., Li, S., Lin, J.S., Sawicki, J.A., and Cotsarelis, G. (2004) Capturing and profiling adult hair follicle stem cells. Nat. Biotech. 22, 411–417.CrossRefGoogle ScholarPubMed
Ohyama, M., Terunuma, A., Tock, C.L., Radonovich, M.F., Pise-Masison, C.A., Hopping, S.B., Brady, J.N., Udey, M.C., and Vogel, J.C. (2006) Characterization and isolation of stem-cell enriched human hair follicle bulge cells. J. Clin. Invest. 116, 249–260.CrossRefGoogle ScholarPubMed
Kim, S.J., Cheung, S., and Hellerstein, M.K. (2004) Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon. Am. J. Physiol. Cell. Physiol. 286, C1464–C1473.CrossRefGoogle ScholarPubMed
Tsujimura, A., Koikawa, Y., Salm, S., Takao, T., Coetzee, S., Moscatelli, D., Shapiro, E., Lepor, H., Sun, T.T., and Wilson, E.L. (2002) Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J. Cell. Biol. 157, 1257–1265.CrossRefGoogle ScholarPubMed
Richardson, G.D., Robson, C.N., Lang, S.H., Maitland, N.J., and Collins, A.T. (2004) CD133, a novel marker for human prostatic epithelial stem cells. J. Cell. Sci. 117, 3539–3545.CrossRefGoogle ScholarPubMed
Lawson, D.A., Xin, L., Lukas, R.U., Cheng, D., and Witte, O.N. (2007) Isolation and functional characterization of murine prostate stem cells. Proc. Natl. Acad. Sci. U. S. A. 104, 181–186.CrossRefGoogle ScholarPubMed
Chambers, I., and Smith, A. (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23, 7150–7160.CrossRefGoogle ScholarPubMed
Tumbar, T., Guasch, G., Greco, V., Blanpain, C., Lowry, W.E., Rendl, M., and Fuchs, E. (2004) Defining the epithelial stem cell niche in skin. Science 303, 359–363.CrossRefGoogle ScholarPubMed
Miller, S.J., Lavker, R.M., and Sun, T.T. (2005) Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim. Biophys. Acta 1756, 25–52.Google ScholarPubMed
Lam, J.S., and Reiter, R.E. (2006) Stem cells in prostate and prostate cancer development. Urol. Oncol. 24, 131–140.CrossRefGoogle ScholarPubMed
Fuchs, E., Tumbar, T., and Guasch, G. (2004) Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778.CrossRefGoogle ScholarPubMed
Moore, K.A., and Lemischka, I.R. (2006) Stem cells and their niches. Science 311, 1880–1885.CrossRefGoogle ScholarPubMed
Reya, T., Morrison, S.J., Clarke, M.F., and Weissman, I.L. (2001) Stem cells, cancer, and cancer stem cells. Nature 414, 105–111.CrossRefGoogle ScholarPubMed
Al-Hajj, M., and Clarke, M.F. (2004) Self-renewal and solid tumor stem cells. Oncogene 23, 7274–7282.CrossRefGoogle ScholarPubMed
Bruce, W.R., and Gaag, H.A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 199, 79–80.CrossRef
Park, C.H., Bersagagel, D.E., and McCulloch, E.A. (1971) Mouse myeloma tumor stem cells: a primary cell culture assay. J. Natl. Cancer Inst. 46, 411–422.Google ScholarPubMed
Wicha, M.S., Liu, S., and Dontu, G. (2006) Cancer stem cells: an old idea – a paradigm shift. Cancer Res. 66, 1883–1890.CrossRefGoogle ScholarPubMed
Bonnet, D., and Dick, J.E. (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737.CrossRefGoogle ScholarPubMed
Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., and Clarke, M.F. (2003) Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 100, 3983–3988.CrossRefGoogle ScholarPubMed
Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004) Identification of human brain tumor initiating cells. Nature 432, 396–401.CrossRefGoogle Scholar
O'Brien, C.A., Pollett, A., Gallinger, S., and Dick, J.E. (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106–110.CrossRefGoogle ScholarPubMed
Ricci-Vitiani, L., Lombardi, D.G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., and Maria, R. (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111–115.CrossRefGoogle ScholarPubMed
Collins, A.T., Berry, P.A., Hyde, C., Stower, M.J., and Maitland, N.J. (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65, 10946–10951.CrossRefGoogle ScholarPubMed
Patrawala, L., Calhoun, T., Schneider-Broussard, R., Li, H., Bhatia, B., Tang, S., Reilly, J.G., Chandra, D., Zhou, J., Claypool, K., Coghlan, L., and Tang, D.G. (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25, 1696–1708.CrossRefGoogle ScholarPubMed
Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821–5828.Google ScholarPubMed
Hemmati, H.D., Nakano, I., Lazareff, J.A., Masterman-Smith, M., Geschwind, D.H., Bronner-Fraser, M., and Kornblum, H.I. (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc. Natl. Acad. Sci. U. S. A. 100, 15178–15183.CrossRefGoogle ScholarPubMed
Kondo, T., Setoguchi, T., and Taga, T. (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc. Natl. Acad. Sci. U. S. A. 101, 781–786.CrossRefGoogle ScholarPubMed
Hirschmann-Jax, C., Foster, A.E., Wulf, G.G., Nuchtern, J.G., Jax, T.W., Gobel, U., Goodell, M.A., and Brenner, M.K. (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc. Natl. Acad. Sci. U. S. A. 101, 14228–14233.CrossRefGoogle ScholarPubMed
Patrawala, L., Calhoun, T., Schneider-Broussard, R., Zhou, J.-J., Claypool, K., and Tang, D.G. (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2− cancer cells are similarly tumorigenic. Cancer Res. 65, 6207–6219.CrossRefGoogle ScholarPubMed
Naumov, G.N., Townson, J.L., MacDonald, I.C., Wilson, S.M., Bramwell, V.H.C., Groom, A.C., and Chambers, A.F. (2003) Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Res. 82, 199–206.CrossRefGoogle ScholarPubMed
Tang, D.G., Patrawala, L., Calhoun, T., Bhatia, B., Schneider-Broussard, R., Choy, G., and Jeter, C. (2007) Prostate cancer stem/progenitor cells: identification, characterization and implications. Mol. Carcinogen. 46, 1–14.CrossRefGoogle ScholarPubMed
Lawson, D.A., and Witte, O.N. (2007) Stem cells in prostate cancer initiation and progression. J. Clin. Invest. 117, 2044–2050.CrossRefGoogle ScholarPubMed
Abate-Shen, C., and Shen, M. (2000) Molecular genetics of prostate cancer. Genes Dev. 14, 2410–2434.CrossRefGoogle ScholarPubMed
Wang, Y., Hayward, S.W., Cao, M., Thayer, K., and Cunha, G.R. (2001) Cell differentiation lineage in the prostate. Differentiation 68, 270–279.CrossRefGoogle ScholarPubMed
Xin, L., Ide, H., Kim, Y., Dubey, P., and Witte, O. (2003) In vivo regeneration of murine prostate from dissociated cell populations of postnatal epithelia and urogenital sinus mesenchyme. Proc. Natl. Acad. Sci. U. S. A. 100, 11896–11903.CrossRefGoogle ScholarPubMed
Aumuller, G., Leonhardt, M., Janssen, M., Konrad, L., Bjartell, A., and Abrahamsson, P.A. (1999) Neurogenic origin of human prostate endocrine cells. Urology 53, 1041–1048.CrossRefGoogle ScholarPubMed
Rizzo, S., Attard, G., and Hudson, D.L. (2005) Prostate epithelial stem cells. Cell Prolif. 38, 363–374.CrossRefGoogle ScholarPubMed
Litvinov, I., DeMarzo, A.M., and Isaacs, J. (2003) Is the Achilles' heel for prostate cancer therapy a gain of function in androgen receptor signaling?J. Clin. Endocrin. Metab. 88, 2972–2982.CrossRefGoogle ScholarPubMed
English, H.F., Santen, R.J., and Isaacs, J.T. (1987) Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement. Prostate 11, 229–242.CrossRefGoogle ScholarPubMed
Sherwood, E.R., Theyer, G., Steiner, G., Berg, L.A., Kozlowski, J.M., and Lee, C. (1991) Differential expression of specific cytokeratin polypeptides in the basal and luminal epithelia of the human prostate. Prostate 18, 303–314.CrossRefGoogle ScholarPubMed
Liu, A.Y., True, L.D., LaTray, L., Nelson, P.S., Ellis, W.J., Vessella, R.L., Lange, P.H., Hood, L., and Engh, G. (1997) Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc. Natl. Acad. Sci. U. S. A. 94, 10705–10710.CrossRefGoogle ScholarPubMed
Signoretti, S., Waltregny, D., Dilks, J., Isaac, B., Lin, D., Garraway, L., Yang, A., Montironi, R., McKeon, F., and Loda, M. (2000) p63 is a prostate basal cell marker and is required for prostate development. Am. J. Pathol. 157, 1769–1775.CrossRefGoogle ScholarPubMed
Collins, A.T., Habib, F.K., Maitland, N.J., and Neal, D.E. (2001) Identification and isolation of human prostate epithelial stem cells based on alpha(2)beta(1)-integrin expression. J. Cell Sci. 114, 3865–3871.Google ScholarPubMed
Kurita, T., Medina, R.T., Mills, A.A., and Cunha, G.R. (2004) Role of p63 and basal cells in the prostate. Development 131, 4955–4964.CrossRefGoogle ScholarPubMed
Burger, P.E., Xiong, X., Coetzee, S., Salm, S.N., Mascatelli, D., Goto, K., and Wilson, E.L. (2005) Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high ability to reconstitute prostatic tissue. Proc. Natl. Acad. Sci. U. S. A. 102, 7180–7185.CrossRefGoogle Scholar
Xin, L., Lawson, D.A., and Witte, O.N. (2005) The Sca-1 cell surface marker enriches for a prostate-regenerating cell population that can initiate prostate tumorigenesis. Proc. Natl. Acad. Sci. U. S. A. 102, 6942–6947.CrossRefGoogle Scholar
Cunha, G.R., and Lung, B. (1978) The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen-insensitive (Tfm) mice. J. Exp. Zool. 205, 181–193.CrossRefGoogle ScholarPubMed
Hayward, S.W., Haughney, P.C., Rosen, M.A., Greulich, K.M., Weier, H.G., Dahiya, R., and Cunha, G.R. (1998) Interactions between human prostatic epithelium and rat urogenital sinus mesenchyme in a tissue recombination model. Differentiation 63, 131–140.CrossRefGoogle Scholar
Bhatt, R.I., Brown, M.D., Hart, C.A., Gilmore, P., Ramani, V.A., George, N.J., and Clarke, N.W. (2003) Novel method for the isolation and characterisation of the putative prostatic stem cell. Cytometry Part A 54, 89–99.CrossRefGoogle ScholarPubMed
Craft, N., Chhor, C., Tran, C., Belldegrun, A., DeKernion, J., Witte, O.N., Said, J., Reiter, R.E., and Sawyers, C.L. (1999) Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res. 59, 5030–5036.Google ScholarPubMed
Pascal, L.E., Oudes, A.J., Petersen, T.W., Goo, Y.A., Walashek, L.S., True, L.D., and Liu, A.Y. (2007) Molecular and cellular characterization of ABCG2 in the prostate. BMC Urol. 7, 6–18.CrossRefGoogle ScholarPubMed
Patrawala, L., and Tang, D.G. (2008) CD44 as a functional cancer stem cell marker and therapeutic target. In: Progress in Gene Therapy: Autologous and Cancer Stem Cell Gene Therapy, vol. 3, pp. 317–334 (Bertolotti, R., and Ozawka, K., eds). Hacxkensack, NJ: World Scientific.Google Scholar
Miki, J., Furusato, B., Li, H., Gu, Y., Takahashi, H., Egawa, S., Sesterhenn, I., McLeod, D., Srivastava, S., and Rhim, J.S. (2007) Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res. 67, 3153–3161.CrossRefGoogle ScholarPubMed
Patrawala, L., Calhoun-Davis, T., Schneider-Broussard, R., and Tang, D.G. (2007) Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+α2β1+ cell population is enriched in tumor-initiating cells. Cancer Res. 67, 6796–6805.CrossRefGoogle ScholarPubMed
Locke, M., Heywood, M., Fawell, S., and Mackenzie, I.C. (2005) Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res. 65, 8944–8950.CrossRefGoogle ScholarPubMed
Li, H., Chen, X., Calhoun-Davis, T., Claypool, K., and Tang, D.G. (2008) PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells. Cancer Res. 68, 1820–1825.CrossRefGoogle ScholarPubMed
Gu, G., Yuan, J., Wills, M., and Kasper, S. (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res. 67, 4807–4815.CrossRefGoogle ScholarPubMed
Gidekel, S., Pizov, G., Bergman, Y., and Pikarsky, E. (2003) Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell 4, 361–370.CrossRefGoogle ScholarPubMed
Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005) Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465–477.CrossRefGoogle ScholarPubMed
Gat, U., DasGupta, R., Degenstein, L., and Fuchs, E. (1998) De novo follicle morphogenesis and hair tumors in mice expressing truncated b-catenin in skin. Cell 95, 605–614.CrossRefGoogle Scholar
Oro, A.E., Higgins, K.M., Hu, Z., Boniface, J.M., Epstein, E.H., and Scott, M.P. (1997) Basal cell carcinomas in mice overexpressing Sonic Hedgehog. Science 276, 817–821.CrossRefGoogle ScholarPubMed
Rossi, D.J., and Weissman, I.L. (2006) Pten, tumorigenesis, and stem cell self-renewal. Cell 125, 229–231.CrossRefGoogle ScholarPubMed
Wang, S., Gao, J., Lei, Q., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G.V., Li, G., Roy-Burman, P., Nelso, P.S., Liu, X., and Wu, H. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209–221.CrossRefGoogle ScholarPubMed
Wang, S., Garcia, A.J., Wu, M., Lawson, D.A., Witte, O.N., and Wu, H. (2006) Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc. Natl. Acad. Sci. U. S. A. 103, 1480–1485.CrossRefGoogle ScholarPubMed
Yardy, G.W., and Brewster, S.F. (2005) Wnt signaling and prostate cancer. Prostate Cancer Prostatic Dis. 8, 119–126.CrossRefGoogle ScholarPubMed
Santagata, S., Demichelis, F., Riva, A., Varambally, S., Hofer, M., Kutok, J.L., Kim, R., Tang, J., Montie, J.E., Chinnaiyan, A.M., Rubin, M.A., and Aster, J.C. (2004) JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res. 64, 6854–6857.CrossRefGoogle ScholarPubMed
Zayzafoon, M., Abdulkadir, S.A., and McDonald, J.M. (2004) Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines. J. Biol. Chem. 279, 3662–3670.CrossRefGoogle ScholarPubMed
Sanchez, P., Hernandez, A.M., Stecca, B., Kahler, A.J., DeGueme, A.M., Barrett, A., Beyna, M., Datta, M.W., Datta, S., and Altaba, A.R. (2004) Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc. Natl. Acad. Sci. U. S. A. 101, 12561–12566.CrossRefGoogle ScholarPubMed
Karhadkar, S.S., Bova, G.S., Abdallah, N., Dhara, S., Gardern, D., Maitra, A., Isaacs, J.T., Berman, D.M., and Beachy, P.A. (2004) Hedgehog signaling in prostate regeneration, neoplasia and metastasis. Nature 431, 707–712.CrossRefGoogle ScholarPubMed
Mora, L.B., Buettner, R., Seigne, J., Diaz, J., Ahmad, N., Garcia, R., Bowman, T., Falcone, R., Fairclough, R., Cantor, A., Muro-Cacho, C., Livingston, S., Karras, J., Pow-Sang, J., and Jove, R. (2002) Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 62, 6659–6666.Google ScholarPubMed
Gao, L., Zhang, L., Hu, J., Li, F., Shao, Y., Zhao, D., Kalvakolanu, D., Kopecko, D., Zhao, X., and Xu, D. (2005) Down-regulation of Signal Transducer and Activator of Transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo. Clin. Cancer Res. 11, 6333–6341.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×