Microecology of the tumour–host invasion field (picture above):
(Invasive carcinoma is viewed as a pathology of multiple cell societies inhabiting the epithelial/mesenchymal stromal unit. Transition to invasive carcinoma is preceded by the activation of host fibroblasts, immune cells and endothelial cells. Invasion occurs in a localized zone of cross-talk and cooperation between the stromal cells and the premalignant epithelium (depicted as zones demarked by dashed lines). Cytokine and enzyme exchange between the participating cells stimulates migration of both cell types towards each other and modifies the adjacent extracellular matrix/basement membrane. The result is a breakdown of normal tissue boundaries)
Molecular cross-talk at the invasion front (picture above):
(Example mediators are shown. Motility and invasion is a bi-directional process. Fibroblasts produce chemoattractants such as SF/HGF, which stimulates motility of tumour cells by binding to the Met receptor (c-Met). Tumour cells produce angiogenesis factors such as VEGF and bFGF, which bind to receptors on stromal vascular cells and cause increased vascular permeability, endothelial proliferation, migration and invasion. Fibroblasts and endothelial stromal cells elaborate latent enzymes, including MMPs and uPA, which dock on the surface of the carcinoma invadopodia and become activated, thereby degrading the ECM, and clearing a pathway. ECM degradation releases bound growth factors such as TGF- and EGF, which bind to cognate receptors (TGF- R and uPAR) on the carcinoma cell. ECM proteolysis also exposes cryptic RGD sites, which are recognized by integrins. Cross-talk between signal pathways within the carcinoma cells links motility, proliferation and pro-survival signals. For example, phosphorylation of FAK through Met and integrin signalling transduces signals through Ras, PI(3)K, -catenin and MLCK, causing cytoskeletal remodelling, ERK activation of mitogenesis, and sustainment of survival through phosphorylation of Akt)
Reference:
Lance A. Liotta etal Progress: The microenvironment of the tumour–host interface Nature 411, 375-379 (17 May 2001)
Epithelia can be reactive to a changing stromal environment (picture above):
(a, Homeostatic interactions between the epithelia and fibroblasts are maintained by positive and negative signals that influence the proliferation and differentiation of both the stroma and epithelia. b, When signalling by a suppressive growth factor (TGF- ) to the stromal fibroblasts is lost (red starburst), it leads to elevated fibroblast proliferation. Resulting paracrine factors (for example, HGF) and potential modifications in the ECM can stimulate the proliferation and transformation of epithelial cells in vivo in some tissues)
Regulation of epithelial growth, differentiation and apoptosis (table)
Reference:
Neil A. Bhowmick etal Stromal fibroblasts in cancer initiation and progression Nature 432, 332-337 (18 November 2004)
While studying the stromal cancer (stem) microenvironment, one area are really fascinating me lot especially their high level of involvement towards identify novel therapeutic targets followed by develop therapeutics, find solutions for various cancers associated problems as well as helping to study the basic of stem-cell biology, etc etc. Such one field is also known as Serine/Threonine Protein Kinases and Tyrosine Protein Kinases.
The surprise thing is that though there are more than 70 numbers of Kinase families playing role within the human system, but just few of them only have been studied (ing), on the field of stroma- cancer cells microenvironment.
Having interest to gain some knowledge on the role of this cross-talk, complex system within the stromal – cancer –microenvironment I would like to begin from the cell fibroblasts (as one of the components of stroma cancer microenvironment ) and its association with kinases.
Since new to this field I would also likes to add the basic, key informative abstracts for further (quickest) reference purpose.
Cross-talk or associated role of fibroblast with stroma components
:- >(pictures above)<-:
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