Cancer-associated Fibroblasts: Is it a key to an intricate lock of
tumorigenesis?
Abstract
The past few decades have witnessed a major leap in knowledge relating
to the role of tumor microenvironment in carcinogenesis and evolving
behaviour of the tumor. Multiple factors within the tumor
microenvironment modulate the cancer cells and the associated therapies.
Stephen Paget first asserted that the microenvironment plays an
important role in the growth of tumor metastasis. The most important
player in the tumor microenvironment is cancer-associated fibroblast
which significantly participates in the proliferation, invasion and
metastasis of tumor cells. Cancer-associated fibroblasts show phenotypic
and functional heterogeneity. Mostly cancer-associated fibroblasts
originate from quiescent resident fibroblast or mesoderm-derived
precursor cells (mesenchymal stem cells), although several alternate
sources of origin have been noted, however, due to a lack of specific
fibroblast-restricted markers, it is very difficult to trace lineage and
identify the biological origin of distinct sub-types of CAFs. CAFs are
predominantly shown by several studies to mainly act as tumor-promoting
agents, however, tumour-inhibiting actions are also being validated by
several studies. A more objectified and comprehensive functional and
phenotypic classification of CAF is required, which will help in better
way for tumor management. Here, in this review, we have tried to review
the current status of CAF origin, along with phenotypic and functional
heterogeneity, and recent progress in cancer-associated fibroblast (CAF)
research.