Involvement of Arp2/3 complex in the process of colorectal carcinogenesis.
Increased motility is one of the characteristics of cancer cells, and actin polymerization and disassembly are essential for cellular motility. Since actin-related protein (Arp) 2/3 complex acts as a nucleus for actin polymerization, in this study, we immunohistochemically investigated the expression of Arp2 and Arp3 in 175 colorectal tumors in various stages of neoplastic progression. Arp2 and Arp3 showed identical expression patterns, and both were expressed in the stromal cells around neoplastic tubules or glands and in the tumor cells themselves. The frequency of expression of Arp2 and Arp3 (Arp2 and 3) by the stromal cells increased with the atypia of the colorectal neoplasms, from 5.5% (3/55) in adenoma with mild or moderate atypia, to 11.8% (2/17) in adenoma with severe atypia, 53.3% (16/30) in intramucosal carcinoma, and 91.8% (67/73) in invasive carcinoma (P<0.0001). The frequency of expression of Arp2 and 3 in the tumor cells was similar and was 1.8% (1/55) in adenoma with mild or moderate atypia, 23.5% (4/17) in adenoma with severe atypia, 23.5% (7/30) in intramucosal carcinoma, and 32.9% (24/73) in invasive carcinoma. Expression of Arp2 and 3 by the stromal cells was significantly correlated with nuclear accumulation of p53 in the tumor cells and stromal expression of CD10. These results suggest that formation of Arp2/3 complex by both neoplastic and stromal cells contributes to the increased motility of both cell types and thus provides suitable conditions for invasion.
Otsubo
Toshiya
T
Department of Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
Iwaya
Keiichi
K
Mukai
Yasuo
Y
Mizokami
Yuji
Y
Serizawa
Hiromi
H
Matsuoka
Takeshi
T
Mukai
Kiyoshi
K
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D015260:Neprilysin / Q000378:metabolism; D011933:Reagent Kits, Diagnostic; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D011933:Reagent Kits, Diagnostic; D015260:Neprilysin