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

Timothy M. Pierpont | Zendy; Amy M. Lyndaker | Zendy; Claire M. Anderson | Zendy; Qiming Jin | Zendy; Elizabeth S. Moore | Zendy; Jamie Roden | Zendy; Alicia M. Braxton | Zendy; Lina Bagepalli | Zendy; Nandita Kataria | Zendy; Hilary Z. Hu | Zendy; Jason Garness | Zendy; Matthew S. Cook | Zendy; Blanche Capel | Zendy; Donald H. Schlafer | Zendy; Teresa Southard | Zendy; Robert S. Weiss | Zendy

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

Author(s) -

Timothy M. Pierpont,

Amy M. Lyndaker,

Claire M. Anderson,

Qiming Jin,

Elizabeth S. Moore,

Jamie Roden,

Alicia M. Braxton,

Lina Bagepalli,

Nandita Kataria,

Hilary Z. Hu,

Jason Garness,

Matthew S. Cook,

Blanche Capel,

Donald H. Schlafer,

Teresa Southard,

Robert S. Weiss

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.10.078

Subject(s) - cancer research , cancer , biology , cancer stem cell , embryonic stem cell , stem cell , testicular cancer , malignant transformation , cancer cell , germ cell , embryonal carcinoma , germ cell tumors , pten , teratoma , chemotherapy , pathology , apoptosis , cellular differentiation , medicine , microbiology and biotechnology , genetics , pi3k/akt/mtor pathway , gene

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.

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