PHILADELPHIA – New findings published in Cancer Research, a journal of the American Association for Cancer Research, advance the current understanding of the role of stem/progenitor cells on the initiation and progression of prostate cancer from the Pten null prostate cancer model.
“Conventional therapy has focused on treating the entire tumor. However, if cancer stem cells are the source of cancer initiation, progression and resistance to therapies, then targeting of these cells may prove more effective in treatment of the lethal phenotype of prostate cancer, termed castrate-resistant disease,” said researcher David J. Mulholland, Ph.D., postdoctoral fellow in the laboratory of Hong Wu, M.D., Ph.D., at the University of California, Los Angeles.
Mulholland, Wu, who is professor of the Institute for Molecular Medicine and Molecular and Medicinal Pharmacology and a researcher at the UCLA’s Jonsson Comprehensive Cancer Center, and colleagues evaluated whether a subpopulation of stem/progenitor cells – Lin-Sca-1+CD49fhigh cells (LSC) – isolated from the Pten null prostate cancer model could initiate tumorgenesis.
After evaluating results from the complementary in vitro and in vivo reconstitution assays, the researchers found that sorted LSC cells retrieved from Pten null spheres or the primary tumors regenerated the cancerous prostate epithelial structure, mimicking the organization of the tumor. The study was conducted in a mouse model.
These results are consistent with, and support the concept that the LSC subpopulation carries tumor-initiating activity. While results from previous studies showed that LSC cells exhibit a stem/progenitor phenotype, the results of this study demonstrate a functional significance of these cells in the etiology of prostate cancer, according to Donald J. Tindall, Ph.D., editorial board member of Cancer Research.
“The significance of these findings is the demonstration that a subpopulation of prostate cells from Pten null mice has the capability of prostate cancer initiation and progression,” said Tindall, professor, director and vice chair of urologic research, and the Carl Rosen professorship in urology in the Departments of Urology and Biochemistry Molecular Biology at the Mayo Clinic College of Medicine.
Wu and colleagues are conducting further studies using drug therapy to target the LSC subpopulation in hopes of achieving greater therapeutic efficacy. Tindall suggested that additional studies are needed to more completely characterize these cells, particularly their role in prostate cancer progression following androgen depletion.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 30,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and nearly 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowship and career development awards. The AACR Annual Meeting attracts more than 16,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.