Research carried out by Prof. Sergio Lamprecht from BGU’s Department of Clinical Biochemistry and Pharmacology and Prof. Alexander Fich, Director of the Institute of Gastroenterology and Hepatology at Soroka University Medical Center, recently published a paper in "Carcinogenesis” entitled “The cancer cells-of-origin in the gastrointestinal tract: progenitors revisited” revealing significant findings pertaining to the 21st century epidemic, cancer.
One of the cardinal questions in cancer research pertains to the identification of the cell that is the initial target of a genetic change. This cell is referred to as cancer cell-of-origin. For a sustained period of time the prevailing view was that adult stem cells are the exclusive cancer cells-of-origin. This tenet was questioned more than a decade ago by Prof. Lamprecht with regard to colon cancer. He proposed on theoretical ground that actively proliferating and differentiated colonic progeny cells could also serve as the initial target cells for transformation outside the stem cell zone and thereby serve- in a defined context -as cancer cells-of- origin. At that time, the hypothesis was highly debated.
Figure 1. Models of tumorigenesis in the colonic crypt initiated by mutant APC.
A large number of subsequent experimental studies have robustly validated the early hypothesis that the first tumorigenic hit may target non-stem progenitor cells not only in the gastrointestinal tract but also in other tissues, and the emerging concept is that stem cells and cancer cells- of- origin do not necessarily denote the same cell type. Remarkably, mounting evidence has shown that normal differentiated cells in response to stem cell ablation or tissue injury are able to acquire stem-cell like properties and to replace the lost cells. This process, aptly defined as plasticity, is also exhibited by cancer non-stem cells that may revert to a stem cell-like state. Prof. Lamprecht and Prof. Fich have examined in depth the new concepts regarding cancer cells-of-origin and progenitor plasticity and have proposed recommendations for future research focused on these fascinating issues.
The findings that non-stem progenitor cells can serve not only as cancer cells-of origin but also act as adult reserve stem cells have wide preventive and therapeutic implications. For instance, anti-cancer protocols designed to “hit” and destroy mutant stem cells should take into consideration the possibility that their vacant place is taken over by cancer non-stem progeny cells.
