Fellows' research: Distinct prognosis of oral cancer patients - Clues from tumor-microenvironment
18 Oct 2018
Dr. Sandeep Singh, Intermediate Fellow
National Institute of Biomedical Genomics, Kalyani
Our group, based at NIBMG, Kalyani, recently discovered the biological basis for variation in prognosis of oral cancer patients. The study published on 05th October 2018 in Oncogenesis, revealed the surprising diversity among fibroblast within the microenvironment of solid tumor mass of oral cancer as responsible factor for distinct behavior of malignant tumor cells.
Several previous studies conducted with oral tumor samples have suggested that the high abundance of activated fibroblasts (marked by alpha-Smooth Muscle Actin, SMA, expression) has been associated with poor-survival of the patients. Conversely, patients with lower abundance of these cells showed better-survival. These observations suggested that the fibroblasts present within oral-tumors are of different properties. Thus, we became interested in studying the molecular and functional differences in cancer-associated fibroblasts from less and more aggressive oral tumors. Dr. P Arun and Dr. Rajeev Sharan as well as pathologist Dr. Indu Arun from Tata Medical Center, Kolkata partnered in this study as clinical collaborators.
Experiments performed with primary oral tumors and the fibroblast derived from these tumors demonstrated the presence of two diverse subtypes of cancer-associated fibroblasts present within these tumors. Cancer-associated fibroblasts were distinct based on differences and expression of various RNA molecules and αSMA stress fibers. Interestingly, the oral-cancer-associated fibroblasts-subtype with lower levels of αSMA was found to exert suppressive effect on the self-renewal growth of oral-stem like cancer cells (SLCCs) by secreting BMP4.
This study suggests that the cancer-associated fibroblasts with myofibroblast phenotype (high-αSMA) provide more conducive environment for aggressive self-renewal of oral-SLCCs through BMP4-downregulation.
Overall, for the first time, we have provided the evidence of a possible evolution of oral tumor microenvironment through myofibroblast differentiation and discovered the CAFs-mediated mechanisms which might restrain cancer cells to a less-aggressive state and better response to the given treatment.
A subtype of cancer-associated fibroblasts with lower expression of alpha-smooth muscle actin suppresses stemness throughBMP4 in oral carcinoma. Ankit Kumar Patel, Kavya Vipparthi, Venu Thatikonda, Indu Arun, Samsiddhi Bhattacharjee*, Rajeev Sharan, Pattatheyil Arun and Sandeep Singh. Oncogenesis, 2018.
*Samsiddhi Bhattacharjee is also an India Alliance Fellow.
Banner image credit: Dr. Sandeep Singh. Immunofluorescence staining for αSMA (green) and vimentin (green) for the established cancer-associated fibroblasts.