We all know about the threat of cancer to human lives. Treating cancer is challenging because it is caused by the abnormality in the body’s own cell. These abnormality helps a cancer cell to grow indefinitely and migrate from its source to a different organ, thereby disturbing its functions. Advancement in cancer research over the years helped in the novel and better drug discovery. Still, we hardly can understand and cure the late stages of cancer.
One important reason for the failure of cancer therapy is the development of multi-drug resistance (MDR) by the cancer cells. MDR is caused by different mechanisms. One of the many ways by which cancer develops MDR is through the formation of giant multinucleated cells (MNCs) (Fig 1b). Giant MNCs have been mainly found in breast, ovarian, colon, lung and blood cancer, particularly after drug treatment.
We have found that about 40%-60% MNCs are present in MDR breast cancer. Although MNCs can give rise to multiple small mononucleated cells, they do not divide, migrate or die for an extended period. During this dormant period, it can, however, secrete some protein factors which are different from its parental cell (cells from which it was formed). During our study, we found that a couple of the proteins (VEGF and MIF) secreted by MNCs, are very important in the context of multi-drug resistance. Secreted VEGF and MIF act on other non-multinucleated cells and activate intracellular p44/42 (protein of a MAP kinase family). Further experiments proved that the action of VEGF and MIF leads to induction of drug resistance in parental cells through p44/42 signal transduction mechanism.
Thus, we concluded that the large MNCs, which was formed as a result of drug-resistance, could activate drug-resistance in other cells with the help of VEGF and MIF. We think that targeting large MNCs is very important to reduce MNCs mediated induction of drug-resistance.
Aditya Parekh did his Ph.D. in Cancer Biology at IIT Kharagpur. He was also a Fulbright Scholar at Johns Hopkins University during his Ph.D.
Dr. Mahitosh Mandal is a Professor at the School of Medical Science and Technology at IIT Kharagpur.