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Modeling high-grade serous ovarian carcinogenesis from the fallopian tube
Open accessAbstract
High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently needed. Progress in these areas is impeded by our poor understanding of HGSOC pathogenesis. Most ovarian cancer research is based on the hypothesis that HGSOC arises from ovarian surface epithelial cells. However, recent studies suggest that >50% of high-grade serous carcinomas involving the ovary likely arise from fallopian tube epithelium. Therefore, limiting HGSOC research to modeling based on ovarian surface epithelium alone is inadequate. To address the need for a fallopian tube-based model of HGSOC, we have developed a system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation. Our model is based on (i) immortalization of FTSECs isolated from primary samples of normal, nondiseased human fallopian tubes, (ii) transformation of FTSECs with defined genetic elements, and (iii) xenograft-based tumorigenic assays. We use our model to show that FTSECs immortalized with human telomerase reverse transcriptase (hTERT) plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-Ras(V12)) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth. Additionally, we demonstrate that FTSECs remain susceptible to c-Myc-mediated transformation in the absence of viral oncoproteins, by replacing SV40 large T and small T antigens with sh-p53, mutant CDK4 (CDK4(R24C)), and sh-PP2A-B56γ. Importantly, all transformed FTSECs gave rise to high-grade Müllerian carcinomas that were grossly, histologically, immunophenotypically, and genomically similar to human HGSOC. With this model, we will now be able to assess the transformative effects of specific genetic alterations on FTSECs in order to characterize their respective roles in HGSOC development.
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“Many, perhaps most, HGSOC originate in the fallopian tube as Serous Tubal Intraepithelial Carcinomas (STICs), shedding onto the surface of the ovary and establishing a tumor (Crum et al., 2007; Karst et al., 2011; Perets and Drapkin, 2016; Zhang et al., 2019).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Karst et al., 2011
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Cites
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345
The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory
Kurman, R. J., & Shih, I. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181cf3d79 · Cited by 1,890
Ras oncogenes: split personalities
Karnoub, A. E., & Weinberg, R. A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2438 · Cited by 1,467
The biology of ovarian cancer: new opportunities for translation
Bast, R. C., Hennessy, B. T., & Mills, G. B. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2644 · Cited by 1,372
Kindelberger, D. W., Lee, Y., Miron, A., Hirsch, M. S., Feltmate, C. M., Medeiros, F., Callahan, M. J., Garner, E. O., Gordon, R. W., Birch, C., et al. (2007) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000213335.40358.47 · Cited by 1,114
Medeiros, F., Muto, M. G., Lee, Y., Elvin, J. A., Callahan, M. J., Feltmate, C. M., Garber, J. E., Cramer, D. W., & Crum, C. P. (2006) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000180854.28831.77 · Cited by 913
A candidate precursor to serous carcinoma that originates in the distal fallopian tube
Lee, Y., Miron, A., Drapkin, R., Nucci, M. R., Medeiros, F., Saleemuddin, A., Garber, J. E., Birch, C., Mou, H., Gordon, R., et al. (2006) · The Journal of Pathology · doi:10.1002/path.2091 · Cited by 904
Self-citationGrading Ovarian Serous Carcinoma Using a Two-Tier System
Malpica, A. L., Deavers, M. T., Lu, K. H., Bodurka, D. C., Atkinson, E. N., Gershenson, D. M., & Silva, E. G. (2004) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200404000-00009 · Cited by 671
Ovarian Low-grade and High-grade Serous Carcinoma
Vang, R., Shih, I., & Kurman, R. J. (2009) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e3181b4fffa · Cited by 562
The Histologic Type and Stage Distribution of Ovarian Carcinomas of Surface Epithelial Origin
Seidman, J. D., Horkayne‐Szakaly, I., Haiba, M., Boice, C. R., Kurman, R. J., & Ronnett, B. M. (2003) · International Journal of Gynecological Pathology · doi:10.1097/01.pgp.0000101080.35393.16 · Cited by 555
Early Events in the Pathogenesis of Epithelial Ovarian Cancer
Landen, C. N., Birrer, M. J., & Sood, A. K. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9970 · Cited by 462
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact
Levanon, K., Crum, C., & Drapkin, R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.1107 · Cited by 412
Self-citationAre All Pelvic (Nonuterine) Serous Carcinomas of Tubal Origin?
Przybycin, C. G., Kurman, R. J., Ronnett, B. M., Shih, I., & VANG, R. S. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181ef7b16 · Cited by 410
Cellular transformation by SV40 large T antigen: interaction with host proteins
Ali, S. H., & DeCaprio, J. A. (2001) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0342 · Cited by 381
The cell of origin of ovarian epithelial tumours
Dubeau, L. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70308-5 · Cited by 363
Identification of specific PP2A complexes involved in human cell transformation
Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00026-1 · Cited by 325
Ovarian Cancer Pathogenesis: A Model in Evolution
Karst, A. M., & Drapkin, R. (2009) · Journal of Oncology · doi:10.1155/2010/932371 · Cited by 310
Self-citationFolkins, A. K., Jarboe, E. A., Saleemuddin, A., Lee, Y., Callahan, M. J., Drapkin, R., Garber, J. E., Muto, M. G., Tworoger, S. S., & Crum, C. P. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.01.012 · Cited by 292
Self-citationA Genetically Defined Model for Human Ovarian Cancer
Liu, J., Yang, G. S., Thompson-Lanza, J. A., Glassman, A. B., Hayes, K. J., Patterson, A. P., Marquez, R. T., Auersperg, N., Yu, Y., Hahn, W. C., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3380 · Cited by 270
PAX8 Reliably Distinguishes Ovarian Serous Tumors From Malignant Mesothelioma
Laury, A. R., Hornick, J. L., Perets, R., Krane, J. F., Corson, J. M., Drapkin, R., & Hirsch, M. S. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181da7687 · Cited by 229
Self-citationHereditary ovarian carcinoma: Heterogeneity, molecular genetics, pathology, and management
Lynch, H. T., Casey, M. J., Snyder, C., Bewtra, C., Lynch, J. F., Butts, M., & Godwin, A. K. (2009) · Molecular Oncology · doi:10.1016/j.molonc.2009.02.004 · Cited by 214
Levanon, K., Ng, V., Piao, H. Y., Zhang, Y., Chang, M. C., Roh, M. H., Kindelberger, D. W., Hirsch, M. S., Crum, C. P., Marto, J. A., et al. (2009) · Oncogene · doi:10.1038/onc.2009.402 · Cited by 213
Self-citationKuo, K., Guan, B., Feng, Y., Mao, T., Chen, X., Jinawath, N., Wang, Y., Kurman, R. J., Shih, I., & Wang, T. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3913 · Cited by 199
Emerging roles for PAX8 in ovarian cancer and endosalpingeal development
Bowen, N. J., Logani, S., Dickerson, E. B., Kapa, L. B., Akhtar, M., Benigno, B. B., & McDonald, J. F. (2006) · Gynecologic Oncology · doi:10.1016/j.ygyno.2006.08.052 · Cited by 199
Rane, S. G., Cosenza, S. C., Mettus, R. V., & Reddy, E. P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.2.644-656.2002 · Cited by 167
Intercepting pelvic cancer in the distal fallopian tube: Theories and realities
Crum, C. P. (2009) · Molecular Oncology · doi:10.1016/j.molonc.2009.01.004 · Cited by 167
Ramakrishna, M., Williams, L. H., Boyle, S. E., Bearfoot, J. L., Sridhar, A., Speed, T. P., Gorringe, K. L., & Campbell, I. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009983 · Cited by 112
Madore, J., Ren, F., Filali‐Mouhim, A., Sanchez, L. M., Köbel, M., Tonin, P. N., Huntsman, D. D., Provencher, D. M., & Mes‐Masson, A. (2009) · The Journal of Pathology · doi:10.1002/path.2659 · Cited by 108
Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes
Sasaki, R., Narisawa‐Saito, M., Yugawa, T., Fujita, M., Tashiro, H., Katabuchi, H., & Kiyono, T. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp007 · Cited by 99
Haverty, P. M., Hon, L., Kaminker, J. S., Chant, J., & Zhang, Z. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-21 · Cited by 96
Nowee, M., Snijders, A., Rockx, D., de Wit, R., Kosma, V.-M., Hämäläinen, K. M., Schouten, J., Verheijen, R. H. M., van Diest, P. J., Albertson, D., et al. (2007) · The Journal of Pathology · doi:10.1002/path.2217 · Cited by 93
Copy Number Analysis Identifies Novel Interactions Between Genomic Loci in Ovarian Cancer
Gorringe, K. L., George, J., Anglesio, M. S., Ramakrishna, M., Etemadmoghadam, D., Cowin, P. A., Sridhar, A., Williams, L. H., Boyle, S. E., Yanaihara, N., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011408 · Cited by 88
Correlations between c-myc gene copy-number and clinicopathological parameters of ovarian tumours
Dimova, I. I., Raitcheva, S., Dimitrov, R., Doganov, N., & Toncheva, D. I. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2005.11.022 · Cited by 48
Darcy, K. M., Brady, W. E., Blancato, J. K., Dickson, R. B., Hoskins, W. J., McGuire, W. P., & Birrer, M. J. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2009.05.012 · Cited by 35
The potential of biologic network models in understanding the etiopathogenesis of ovarian cancer
Khalil, I. G., BREWER, M. A., Neyarapally, T. A., & Runowicz, C. D. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2009.10.085 · Cited by 31
Zheng, J., Mercado‐Uribe, I., Rosen, D. G., Chang, B., Liu, P., Yang, G. S., Malpica, A. L., Naora, H., Auersperg, N., Mills, G. B., et al. (2010) · Cell Cycle · doi:10.4161/cc.9.1.10264 · Cited by 16
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Metadata
- Authors
- Karst, A. M., Levanon, K., & Drapkin, R.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-04-18
- Volume
- 108
- Issue
- 18
- Pages
- 7547-7552
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3088633
- OpenAlex
- W2071014344
- Cited by
- 280
- References
- 37
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 6 · 2023: 14 · 2022: 9 · 2021: 19 · 2020: 12 · 2019: 22 · 2018: 22 · 2017: 11 · 2016: 25 · 2015: 28 · 2014: 30 · 2013: 27 · 2012: 26
- FWCI
- 34.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- National Cancer Institute (P50CA105009)
- Topics
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- high-grade serous ovarian cancer, fallopian tube epithelium, secretory epithelial cells, carcinogenesis, cell transformation, hTERT immortalization, oncogenic Ras, c-Myc, p53, CDK4, Müllerian carcinoma, xenograft tumorigenicity, ovarian surface epithelium
- MeSH terms
- Antigens, Polyomavirus Transforming, Carcinoma, Cell Transformation, Neoplastic, Epithelial Cells, Fallopian Tubes, Female, Humans, Immunohistochemistry, Microscopy, Fluorescence, Ovarian Neoplasms, Tumor Stem Cell Assay, Blotting, Western, Carcinogenicity Tests, Telomerase, Cell Line, Tumor, Comparative Genomic Hybridization
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