Cancer cells propagated from early prostate cancer

September 25, 2013

A team of cancer researchers at the University of California, San Diego has identified the existence of precursor cells in early prostate cancers. These cells are resistant to androgen-deprivation therapy, and may drive the subsequent emergence of recurrent or metastatic prostate cancer.

The scientists' findings, suggesting that potentially lethal castration-resistant prostate carcinoma cells already exist in some cancer patients at the very early stages of their disease, will be published by PLOS ONE on September 25, 2013.

The work describes the isolation and propagation of the earliest prostate cancer cells yet identified in human prostate cancer biopsy samples, allowing the detailed molecular characterization of these very early-stage cancer cells, including analysis of gene expression and mutations.

"Full molecular characterization of the earliest prostate cancer cells will facilitate identification of pharmacological approaches which are not currently available," said Martin Haas, PhD, professor of biology and oncology at UC San Diego Moores Cancer Center. "Development of such early-stage treatments could reduce the incidence of cancer progression to recurrent invasive or metastatic disease."

Treatments for prostate cancer often target androgen pathways. Androgens are male hormones, such as testosterone, that research shows can feed prostate tumors. Castration-resistant (CR) prostate cancer is prostate cancer that has become resistant to medical or surgical treatments that lower testosterone.

The UC San Diego researchers, including Stephen M. Baird, MD, and Daniel J. Donoghue, PhD, isolated a class of prostate cancer cells from early-stage human prostate carcinomas that had been removed by surgical prostatectomy and cultured the cells in a synthetic medium devoid of steroid hormones. In this way, early prostate cancer cells (CR-PrCA) were isolated from dozens of early Stage I prostate carcinoma cases.

When transplanted into the anterior prostates of male SCID mice the cultured cells generated locally invasive human prostate cancers. In castrated mice, in the absence of androgen, the cells grew locally as non-differentiated human cancer cells.

Extensive characterization of these CR-PrCa cells has shown them to share characteristics with multipotent cancer stem or progenitor cells that possess basal prostate cell characteristics.

"One interpretation of our data suggests that the culture-isolated CR-PrCa cells are precursors which, after additional progression steps, would lead to recurrent invasive or metastatic disease," said Haas. "In fact, the cancers that were generated by transplantation into intact SCID mice of the cultured human CR-PrCa cells were pathologically indistinguishable from the original cancer tissue from patients used to grow the cells in culture," he explained.

The hope is that possible future treatments targeting these early-stage prostate cancer precursor cells might increase cures and improve long-term survival rates.

According to the American Urological Association, prostate cancer is the most commonly diagnosed solid organ malignancy in the United States and remains the second leading cause of cancer deaths among American men. Approximately 240,000 new diagnoses of prostate cancer and over 28,000 deaths were estimated in the U.S. in 2012.
-end-
Additional contributors to the study include Rita R. Fiñones, PhD, Jo Yeargin, Melissa Lee, Aman Preet Kaur, Clari Cheng, Paulina Sun, Christopher Wu, Catherine Nguyen, Jessica Wang-Rodriguez, MD and April N. Meyer, all of UC San Diego.

The study was funded by the UC San Diego Foundation.

University of California - San Diego

Related Prostate Cancer Articles from Brightsurf:

Low risk of cancer spread on active surveillance for early prostate cancer
Men undergoing active surveillance for prostate cancer have very low rates - one percent or less - of cancer spread (metastases) or death from prostate cancer, according to a recent study published in the Journal of Urology®, an Official Journal of the American Urological Association (AUA).

ESMO 2020: Breast cancer drug set to transform prostate cancer treatment
A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.

Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.

The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.

Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.

First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.

Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.

CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.

Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.

Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.

Read More: Prostate Cancer News and Prostate Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.