| RRC ID |
52005
|
| Author |
Kanemaru A, Yamamoto K, Kawaguchi M, Fukushima T, Lin CY, Johnson MD, Camerer E, Kataoka H.
|
| Title |
Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer-associated fibroblasts by paracrine activation of protease-activated receptor 2.
|
| Journal |
Int J Cancer
|
| Abstract |
Cancer-associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI-1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI-1-insufficiency contributes to CAF recruitment in OSCC. Serum-free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI-1-knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease-activated receptor-2 (PAR-2) expression in NB1RGB and MRC5, but not in KD, and a PAR-2 antagonist blocked the stimulatory effect of HAI-1 knockdown on migration of the PAR-2 expressing cell lines. Moreover, HAI-1-deficient SFCM showed additive stimulatory effects on the migration of wild-type but not PAR-2-deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI-1-insufficiency was mediated by PAR-2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR-2 agonist protease. HAI-1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI-1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by paracrine activation of fibroblast PAR-2. Immunohistochemical analysis of resected OSCC revealed increased PAR2-positive CAFs in 35% (33/95) of the cases studied. The increased PAR-2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease-free survival of the patients.
|
| Volume |
140(1)
|
| Pages |
130-141
|
| Published |
2017-1-1
|
| DOI |
10.1002/ijc.30426
|
| PMID |
27615543
|
| MeSH |
Adult
Aged
Aged, 80 and over
Cancer-Associated Fibroblasts / pathology*
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Movement / drug effects
Cells, Cultured
Culture Media, Conditioned / pharmacology
Culture Media, Serum-Free / pharmacology
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Male
Membrane Proteins / metabolism*
Middle Aged
Mouth Neoplasms / genetics
Mouth Neoplasms / metabolism
Mouth Neoplasms / pathology*
Paracrine Communication
Proteinase Inhibitory Proteins, Secretory / genetics*
Receptor, PAR-2 / metabolism*
Serine Endopeptidases / metabolism*
|
| IF |
5.145
|
| Times Cited |
17
|
| Resource |
| Human and Animal Cells |
NB1RGB(RCB0222) |
