The signaling adapter protein PINCH is up-regulated in the stroma of common cancers, notably at invasive edges.
BACKGROUND
PINCH is an LIM (double zinc finger domain) protein that functions as an adapter at a key convergence point for integrin and growth factor signal transduction. Because no information is available regarding its expression in vivo in human tissues, this study evaluated the distribution and abundance of PINCH in patients with breast, prostate, lung, colon, and skin carcinomas.


METHODS
A polyclonal antibody was raised to a purified 6-histidine PINCH fusion protein and used to evaluate 74 cases comprising 33 breast carcinomas (21 ductal carcinomas, 6 lobular carcinomas, 4 ductal carcinomas in situ, 2 lobular carcinomas in situ), 22 prostate carcinomas, 5 colon carcinomas, 6 lung carcinomas (3 adenocarcinomas and 3 squamous carcinomas), and 8 skin carcinomas (4 basal cell carcinomas and 4 squamous cell carcinomas) by immunoperoxidase histochemistry of formalin-fixed, paraffin-embedded tissues. Lysates of frozen tissue from the epithelium of two normal breasts and six breast carcinomas were evaluated by immunoblotting.


RESULTS
Immunostaining for PINCH was increased in the cytoplasm of fibroblastoid cells in areas of the tumor-associated stroma in all carcinomatous tissues evaluated. The most intense stromal immunostaining for PINCH was noted at invasive edges, particularly in breast carcinomatous tissue. Immunoblotting of lysates from normal breast and breast carcinomatous tissue confirmed that PINCH protein expression was markedly increased in breast carcinomatous tissues.


CONCLUSIONS
PINCH is up-regulated in tumor-associated stromal cells, particularly at invasive edges, and may be a marker for stroma manifesting the ability to facilitate invasion. Because of this and because PINCH functions as a "molecular switch" in signal transduction, PINCH may be a new target for drug discovery aimed at the tumor-associated stroma.
Wang-Rodriguez
Jessica
J
Department of Pathology, University of California, San Diego, La Jolla 92093, USA.
Dreilinger
Anna D
AD
Alsharabi
Ghazwan M
GM
Rearden
Ann
A
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002278:Carcinoma in Situ / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism*; D016612:Paraffin Embedding; D011471:Prostatic Neoplasms / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins