Survey Part- A ] Serine/Threonine and Tyrosine Protein Kinases in "Fibroblast" of Stroma (cancer) Microenvironment

Independent role of Serine/Threonine and Tyrosine Protein Kinases in "Fibroblast" of Stroma (cancer) Microenvironment:


e) Churg-Strauss syndrome (CSS): is a systemic disease that shows marked eosinophilia along with eosinophil infiltration in the tissue. Prolonged eosinophil survival plays an important role in the pathogenesis of CSS(1), which is also invole development of lipoma, a very rare benign tumor of the tracheobronchial tree(2).

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase, and its ligand is collagen. DDR1 was expressed in human leukocytes and fibroblasts, and it plays an important role in leukocyte cytokine production and fibroblast survival in an NF-kappaB-dependent manner, as well as (DDR1) contributes to the eosinophil survival in the tissue microenvironment of CSS and that it might be involved in the development of CSS.

References:
1 Matsuyama W etal Discoidin domain receptor 1 contributes to eosinophil survival in an NF-kappaB-dependent manner in Churg-Strauss syndrome Blood. 2007 Jan 1;109(1):22-30..

2 Ergan-Arsava B etal Endobronchial lipoma in a patient with Churg-Strauss syndrome Thorac Cardiovasc Surg. 2006 Jun;54(4):283-5.


f) inducible fibroblast growth factor receptor-1 (iFGFR1):
Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, the authors discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response, which induced recruitment of macrophages (responsible for preneoplastic progression) to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Further more studies also showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro.

Reference:
Schwertfeger KL etal A critical role for the inflammatory response in a mouse model of preneoplastic progression Cancer Res. 2006 Jun 1;66(11):5676-85


g) isozyme of 6-phosphofructo-2 kinase (iPFK-2):

Tumor cells maintain an especially high glycolytic rate to supply the anabolic precursors essential for de novo nucleotide synthesis. We recently cloned an inducible isozyme of 6-phosphofructo-2 kinase (iPFK-2) that bears an oncogene-like regulatory element in its mRNA and functions to produce fructose-2,6-bisphosphate, which is a powerful allosteric activator of glycolysis. Rapidly proliferating cancer cells constitutively express iPFK-2 in vitro, and inhibition of iPFK-2 expression decreases tumor growth in experimental animal models.

In particular, iPFK-2 expression was found to be markedly elevated in multiple aggressive primary neoplasms, including colon, breast, ovarian, and thyroid carcinomas. iPFK-2 mRNA and protein expression were induced by hypoxia in cultured human colon adenocarcinoma cells, and an examination of normal lung fibroblasts showed that iPFK-2 and fructose-2,6-bisphosphate levels increased specifically during the S phase of the cell cycle. These data indicate that iPFK-2 is abundantly expressed in human tumors in situ and may serve as an essential regulator of glycolysis during cell cycle progression and growth in an hypoxic microenvironment.


Reference:
Atsumi T etal High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers Cancer Res. 2002 Oct 15;62(20):5881-7



-> to be continued..;becasue of likes to do some correlated studies---<-