Biomarker Links Clinical Outcome of Lethal Tumor Metabolism

The tumor microenvironment plays a critical role not only in early oncogenesis, but also in tumor progression as well as in the response of cancer cells to therapy, and therefore it is important to study both the malignant tissue and the surrounding stroma.

Scientists at the Kimmel Cancer Center (Philadelphia, PA, USA) implemented a retrospective analysis of over 180 women with triple negative breast cancer, one of the most deadly forms of breast cancers, with fast-growing tumors that often affect younger women. Tumor tissue-microarrays were constructed using a commercial tissue arrayer. Polyclonal antibodies were used for the specific immunostaining on tissue sections of the metabolic biomarker monocarboxylate transporter 4 (MCT4) and caveolin-1 (Cav-1).

Analyzing the human breast cancer samples, the team found that women with high levels of stromal MCT4 and a loss of stromal Cav-1 had poorer overall survival, consistent with a higher risk for recurrence, metastasis, and treatment failure. The findings suggest that when used in conjunction with the stromal Cav-1 biomarker, which the authors point out has been independently validated by six other groups worldwide, MCT4 can further stratify the intermediate-risk group into high and low risk.

Today, no such markers are applied in care of triple negative breast cancer, and as a result, patients are all treated the same. Identifying patients who are at high risk of failing standard chemotherapy and poorer outcomes could help direct them sooner to clinical trials exploring new treatments, which could ultimately improve survival. The tissue arrayer instrument used in the study was manufactured by Veridiam (Oceanside, CA, USA) and the anti-Cav-1 polyclonal antibodies are a product of Santa Cruz Biotech (Santa Cruz, CA, USA).

Michael P. Lisanti, MD, PhD, a lead author of the study, said, "The whole idea is that MCT4 is a metabolic marker for a new model of tumor metabolism and that patients with this type of metabolism are feeding their cancer cells. It is lethal and resistant to current therapy. This paper is the missing clinical proof for the paradigm shift from the "old cancer theory" to the "new cancer theory," known as the "Reverse Warburg Effect." The new theory being that aerobic glycolysis actually takes place in tumor-associated fibroblasts, and not in cancer cells, as the old theory posits. The study was published on March 15, 2012, in the journal Cell Cycle.

Related Links:
Kimmel Cancer Center
Veridiam
Santa Cruz Biotech