Monday, July 8, 2013

WCMC-Q researchers tackle ever increasing breast cancer scourge

Breast cancer ranks among the most pernicious diseases affecting women, with one in eight at risk by the age of 70.

The World Health Organization (WHO) rates breast cancer is the most common cancer in women worldwide and the main cause of death from cancer among women globally. Despite the high incidence rates in Western countries, 89 percent of women diagnosed with breast cancer are still alive five years after their diagnosis. This is due to early detection and treatment.

Latest research figures from the National Cancer Institute in the US estimate that in early 2013 there are already 232,340 women and 2,240 men who presented with new cases of breast cancer in the United States and a staggering 39,620 women and 410 men have already died this year from breast cancer.

Breast cancer is defined as cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare. 

It comes then as no surprise that researchers, laboratories and health academics around the globe have turned the focus of attention on this problem by seeking to provide improved treatment, greater knowledge, better diagnostics and dare to even suggest; a solution to the disease. At Weill Cornell Medical College in Qatar (WCMC-Q) the Tabrizi stem cell and microenvironment laboratory under the leadership and direction of Associate Professor of Genetic Medicine Jeremie Arash Tabrizi, is undertaking impressive breast cancer research.

Pegah Ghiabi is a researcher on the team and a PhD student whose work focuses on breast cancer and its microenvironment.  “The focus of my work is on studying tumor microenvironment effect on breast cancer progression, stemness and metastasis,” Pegah said.

Her work has already attracted high-level academic interest. At a recent award ceremony, hosted by Qatar Foundation for Education, Science and Community Development held at Qatar National Convention Centre, the venue of Qatar International Conference on Stem Cell Science and Policy, she was recognized for excellence in stem cell research, with the research exhibited through poster presentations during the conference. Pegah received an award for her poster presentation on research into therapy to inhibit the cancer stem cell population aiming at preventing the recurrence of breast cancer.

The WHO warns that the incidence of breast cancer is increasing in the developing world due to increase life expectancy; increase urbanization and adoption of Western lifestyles. Although some risk reduction might be achieved with prevention, these strategies cannot eliminate the majority of breast cancers that develop in low- and middle-income countries where breast cancer is diagnosed in very late stages. Therefore, early detection in order to improve breast cancer outcome and survival remains the cornerstone of breast cancer control.

“One of the components of the tumor microenvironment that I am interested in is the endothelial cells,” Pegah said. “These cells are the building blocks of blood vessels; however, recently scientists have shown that in addition to acting as conduits for oxygen and nutrients, they are responsible for regulating tumor growth by secreting several growth factors.”

“In order to study how endothelial cells affect breast cancer progression, I have designed several co-culture experiments by mixing breast cancer and endothelial cells together in the laboratory.  After several days of co-cultivation, breast cancer cells were separated from endothelial cells by flow cytometry and their functional properties were assessed.  Interestingly, endothelial cells were capable of enhancing breast cancer cell growth, invasiveness, and metastatic properties.   Most importantly, endothelial cells enhanced the cancer stem cell population of breast cancer cells.  This is noteworthy because breast cancer stem cells, like any other cancer stem cells, are responsible for cancer re-initiation after therapy. If we can eliminate this small population by blocking their interaction with endothelial cells, we are capable of coming up with more effective therapy approaches to combat cancer.”

Pegah said another aspect of her work focuses on how breast cancer cells induce endothelial cells to undergo phenotypic changes that make them more potent in supporting tumor progression.  “My initial observations support our hypothesis on the involvement of breast cancer cells in deriving endothelial cells into fibroblasts that can actually help cancer cells grow better.”

Pegah’s work on the reciprocal interaction between endothelial and breast cancer cells is done in the Stem Cell & Microenvironment Laboratory, WCMC-Q and Paris XI University, Paris, France and will be published in the near future.

The work determines a role for tumor microenvironment (niche) in cancer progression that has been recently indicated. Several components reside in the niche that is partly responsible for the survival advantages acquired by tumor cells.  Among them, endothelial cells -- the building blocks of tumor vasculature   -- have been shown to have additional benefits than merely a conduit for supplying oxygen and nutrients.  Here, we intend to show the critical role of the Akt-activated endothelial cells (E4ORF1) on breast cancer development, survival and invasiveness.  Breast cancer cell (BCC) and cancer stem cell (BCSC) proliferation was measured by co-cultivating E4ORF1 with BCCs under adherent and non-adherent conditions.

Furthermore, BCSC enrichment by E4ORF1 was evaluated by analyzing the CD44+/CD24Low/- population of BCCs by FACS and by assessing the expression of pluripotency markers using RT-PCR.  BCSCs resistance to drugs was investigated by addition of metformin drug in the presence/absence of E4ORF1.

The involvement of E4ORF1 in BCC metastasis was shown by scratch and adhesion assays with/out E4ORF1 cells.  The results demonstrated that E4ORF1 was capable of conferring survival advantages to tumor cells including a 5-fold increase in the self-renewal capacity of BCCs and BCSCs; 4-fold increase in CD44+/CD24Low/- population; up-regulation of pluripotency markers; a 2.5-fold increase in survival rate of BCSCs; and enhanced invasion/adhesion property of BCCs.

The data suggest a major role for E4ORFl in BC progression, stemness, resistance and metastasis.  This characteristic of E4ORF1 cells can be exploited in developing novel therapy approaches to combat BC more effectively.

Associate Professor Rafi says Pegah’s work perfectly integrates in the scope of the laboratory. “Indeed, despite tremendous progresses in cancer therapies the mortality still remains high. Recently many groups have illustrated the role of the host (microenvironment) in nurturing tumor cells. The Rafi laboratory focuses on the interaction between cancer cells and normal cells of the body. Pegah’s work conforms to similar findings we have in ovarian cancer and helps in defining new therapeutic strategies that will disrupt the cross talk between cancer and normal cells.

“Focusing on breast and ovarian cancer is quite logical as these are the most frequent and the most deadly cancers affecting women. When we consider the role of women in our societies (often being the core of the family) a cancer is not only tragic for the patient but also devastating at the family level.

“We are therefore trying to have a group of solid scientists that unite their effort to find new solutions today and maybe the cure one day to this terrible disease,” Dr. Rafi said.

[1158 words]

No comments:

Post a Comment