In a breakthrough that could impact the course of research to find a cure to cancer, researchers based in Guwahati, Assam, in collaboration with their US partners, have found that cancer stem cells (CSCs) activate a stemness pathway, which may help cancer cells to escape from chemotherapy/radiotherapy.
This same stemness pathway was activated by embryonic stem cells exhibiting altruistic behavior, with the current finding pointing to a possible role of biological altruism in cancer growth, a possibility that may opens up a whole new dimension in cancer biology.
The study, carried out by physician scientist Bikul Das and his research team at KaviKrishna Lab in Guwahati, has been published online by the journal ‘Cancer Research’, published by the American Association for Cancer Research.
“The incidence of cancer is rapidly rising in India, mainly in the Northeast region of the country where KaviKrishna laboratory is located. However, treatment against cancer is not yet successful. This is largely attributed to the cancer stem cell ability to stay quiescent (low frequency), and then escape chemotherapy/radiation,” he explained.
Das further said many cancer types including leukemia (blood cancer) contain a rare fraction of CSCs capable of regenerating the cancer, while the rest of the cancer cells are not endowed with the capacity to relapse. These CSCs are secured as immune cells and chemotherapy / radiation cannot destroy these cells, and more importantly, these CSCs have the unique ability to maintain a low but stable frequency among the millions of cancer cells, across generations.
The phenomena of CSC being rare goes against the dogma that cancer is largely a disease of Darwinian evolution, but may be explained in terms of biological altruism (group selection), Das added.
However, it has been challenging to find the molecular mechanisms of how CSCs retain a stable frequency across generations despite mutations/microenvironmetal stress.
Earlier research by Das had revealed that some human embryonic stem cells activate a molecular signaling pathway, the HIF-2alpha stemness pathway to reprogram themselves to exhibit altruism, i.e. sacrificing self-fitness for the sake of group fitness, which led him to suspect that CSCs may hijack the same HIF-2alhpa stemness pathway to maintain a stable frequency across the generations.
“From our previous research, we learned that HIF-2alhpa pathway maintain the stemness of altruistic stem cells obtained from embryonic stem cells. So, we hypothesized that like altruistic stem cells, CSCs may also have figured out the advantage of using the HIF-2alpha stemness pathway,” he added.
To test this hypothesis, Das and his collaborators at Stanford University, utilized a well-known mouse model of MYC induced lymphoma cancer, developed by Dean Felsher of Stanford University, and to confirm the findings in clinical subjects, the research team also collaborated with B Borooah Cancer Institute & Research Centre, Guwahati, and Gauhati University, Guwahati.
Das along with his group found that lymphoma stem cells hijack the altruistic stemness pathway of embryonic stem cells to maintain their rare identity among millions of non-stem cancer cells.
“Significantly, this new study is helping to shed light on the mechanisms that endow the cancer stem cells to maintain a low but stable frequency across generations,” Das said.
Claiming that these findings have the potential of re-defining the way cancer growth is currently understood, Dr Das said, “Biological altruism may have a role in CSC maintenance and in cancer growth.”
The success of this international collaborative study is now encouraging the team to move one step forward to understand cancer through biological altruism, an area where KaviKrishna lab and its sister lab at Boston, the Thoreau Lab for Global Health, are taking leadership role.
Das is the co-senior and co-corresponding author of the study, while Dean W Felsher, professor of Medicine and Patholgy, Stanford University School of Medicine, is the co-senior author of the study.
The research team at KaviKrishna Lab included graduate students Bidisha Pal, Seema Bhuyan, Joyeeta Talukdar, Sora Sandhya and Sukanya Gayan.
The research was funded by the KaviKrishna Foundation (Sualkuchi, India), the Laurel Foundation (Pasadena, California), and NIH-RO1.