Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.

Published

Journal Article

Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size but also selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy.

Full Text

Duke Authors

Cited Authors

  • Pierpont, TM; Lyndaker, AM; Anderson, CM; Jin, Q; Moore, ES; Roden, JL; Braxton, A; Bagepalli, L; Kataria, N; Hu, HZ; Garness, J; Cook, MS; Capel, B; Schlafer, DH; Southard, T; Weiss, RS

Published Date

  • November 14, 2017

Published In

Volume / Issue

  • 21 / 7

Start / End Page

  • 1896 - 1909

PubMed ID

  • 29141221

Pubmed Central ID

  • 29141221

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.10.078

Language

  • eng

Conference Location

  • United States