Background: Prostate cancer (PCa) is a clinically and molecularly heterogeneous disease, with differences in incidence and mortality among and between racial groups, which are only partially predicted by grade and stage. Age-adjusted incidence and mortality rates for PCa among African American (AA) men are 1.6- and 2.4-fold greater, respectively, than among white men. Preclinical models of AA PCa, including cell lines and xenografts, are severely lacking. This work addresses the urgent need to generate such models for study of the biology of AA PCa and for testing of novel therapeutic agents in models that are expected to be reflective of the clinical setting.
Methods: To generate AA PCa patient-derived primary cell lines, we have used the fibroblast feeder cell system established at Georgetown University. In this method, human tumor cells are cocultivated with irradiated mouse fibroblasts in medium with addition of ROCK inhibitor. For generation of AA PCa patient-derived xenografts, we have collected sections of human prostate tumors, minced, suspended, and implanted in the renal capsule of immunodeficient mice. Tumor specimens have been collected and formalin-fixed, paraffin-embedded for histologic evaluation. Sections of such blocks have been stained using hematoxylin and eosin. DNA from the tumor specimens has been used to perform ancestral genotyping.
Results: We have established eight AA PCa patient-derived primary cell lines and two AA PCa patient-derived xenografts. The AA PCa patient-derived primary cell lines have grown throughout the feeder layer and directly onto the plastic of the flasks. Currently, these lines are growing without addition of fibroblast feeder cells. The two AA PCa patient-derived xenografts have been passaged beyond three generations and key histologic features have been found to be consistent between the patient tumor and the patient-derived explant. In addition, African ancestry of the patient has been confirmed by ancestral genotyping. Further studies to more fully characterize the AA PCa patient-derived primary cell lines and xenografts at the pathologic, biologic, and molecular levels are currently under way. Procurement of individual AA PCa patient tissues continues for establishment of additional AA PCa patient-derived primary cell lines and xenografts.
Conclusions: Strategies designed to maximize PCa specimen availability and tumor content enable the establishment of AA PCa patient-derived primary cell lines and xenografts. Such preclinical models of AA PCa will enable a more rigorous interrogation of the molecular mechanisms underlying AA PCa and aid in the development of new biomarkers and therapeutic agents for AA PCa.
Citation Format: Brendon Patierno, Wayne Glover, Thomas Ribar, Rick Kittles, Wen-Chi Foo, Shannon McCall, Jiaoti Huang, Daniel George, Jennifer Freedman, Steven Patierno, Kris Wood, David Hsu. Establishment of African American prostate cancer patient-derived primary cell lines and xenografts [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A79.