Dr. Weeks’ Comment: Obesity and inflammation are both mutually destructive forces which worsen cancer. SOUL, the powerful drink made from the three anti-inflammatory seeds – black cumin, black raspberry and the resveratrol rich Chardonnay grape – is a must for people fighting cancer. In addition: exercise! and oxygenate your blood and drink healthy water. For more information on Corrective Cancer Care, read here
Obesity has been linked to poor prognosis in post-menopausal women with breast cancer, the most common invasive cancer in women. Adipose stem cells (ASCs), which are recruited to sites of inflammation including tumors, play a role in breast cancer progression, but it is not clear whether this contributes to the impact of obesity on prognosis. However, it is known that ASCs isolated from individuals with different body mass indices have different gene expression profiles, including genes involved in angiogenesis, secretory pathways, and tissue invasion. There is also evidence that ASCs from different parts of the body have different impacts on breast cancer.
In a study published in Breast Cancer Research, Bruce Bunnell and colleagues from Tulane University, USA, examined the effect of ASCs on breast cancer cell lines and in immunocompromised SCID/beige mice. The ASCs were isolated from the abdomen and other tissue sites of both obese and non-obese women. They found that ASCs from obese women – but not non-obese women – induce enhanced proliferation of MCF7 breast cancer cells when these cells were cultured together. The same effect was observed when MCF7 cells were cultured in ASC-conditioned media.
Further analysis revealed that the expression of 13 genes known to be involved in breast cancer progression is altered in MCF7 cells grown in media conditioned with non-abdominal ASCs from obese women. These include genes involved in apoptosis, angiogenesis and metastasis. Culturing MCF7 cells with abdominal ASCs from obese women altered the expression of a further 14 genes, including genes involved in the cell cycle and adhesion, as well as additional apoptosis and metastasis genes. Western blot analysis confirmed increased protein expression from a selection of these genes.
Bunnell and colleagues then went on to show that co-injection of MCF7 cells with ASCs into the mammary fat pad of SCID/beige mice led to increased tumor volume compared to MCF7 cells alone, but only in the presence of estrogen, suggesting that estrogen may influence tumor growth by activating ASCs. An increase in tumor size was observed regardless of the obesity status of the women or the site of origin of the ASCs. However, abdominal ASCs from obese women resulted in larger tumors than ASCs from non-obese women or non-abdominal ASCs from obese women, suggesting that ASCs are conditioned by the microenvironment of their site of origin and this may influence their impact on tumor cells.
Gene expression analysis revealed that both site of origin and obesity status of the subjects influences the gene expression profiles of ASCs, with abdominal ASCs from obese women showing the most robust changes in expression in leptin and thyrotropin-releasing hormone. Finally, the authors illustrated that estrogen stimulates the production of leptin by ASCs, which in turn stimulates MCF7 cell proliferation.
These findings not only suggest a mechanism to explain the impact of obesity on prognosis in women with breast cancer, but also suggest that leptin may be a novel therapeutic target for treating breast cancer.
Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways