Friday, June 4, 2010

Stem cell biology challenges traditional view of tumorigenesis

A very interesting aspect of stem cell biology is the hypothesis that stem cells and progenitors may be the origin of some cancers.  Below is an excerpt from the research group web page of Dr. Eva Hernando.  I believe this sums up the current views on this subject quite nicely.
Traditionally, mature cells in specific tissues and organs have been regarded as the cell-of-origin of the corresponding tumors. However, the observation that tumor cells need to accumulate genetic and phenotypic alterations over extended time periods has turned the view in recent years to stem cells or progenitors with a prolonged lifespan, broadly distributed in local reservoirs [1]. These cells, in charge of maintaining tissue homeostasis, are now considered as the potential target of neoplastic transformation.

Although this notion has been largely accepted for certain leukemias and lymphomas in which the corresponding hematopoietic progenitors are precisely defined, this theory has not yet permeated the field of solid tumors, with few exceptions [2-4]. The identification of maturation stages in non-hematopoietic (i.e., epithelial, mesenchymal) cell types is proving difficult due to the lack of distinctive markers and the low abundance of such intermediates in adult tissues, except after trauma-induced regeneration.

Our laboratory is studying whether certain sarcomas originate from mesenchymal progenitors [5, 6] and whether melanomas result from transformation of melanocytic precursors [7, 8]. Moreover, we hypothesize that alterations in the normal differentiation process of these progenitors act at early stages of tumor initiation, and that the retention or reactivation of stem cell properties may contribute to tumor progression and aggressive behavior (resistance to therapy, metastasis). A limitation for these studies is our partial understanding of the normal differentiation process of these two lineages.
The stem cell state and the process of differentiation are regulated in part by signalling pathways, many of which are a function of kinase activity.  Will we be able to target these stem cell specific pathways with small molecule inhibitors to prevent cancers?

1 comment:

Will H said...

Is there anyway to spur a reversal of "the lack of distinctive markers and the low abundance of such intermediates in adult tissues" with the hope of creating ways to ID these, without trauma?