Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells.
BACKGROUND
CXCR4, the chemokine receptor for CXCL12, has recently been involved in the metastatic process of several neoplasms.


METHODS
The expression of CXCR4 was evaluated by immunohistochemistry of colorectal tissue samples and by flow cytometry on Caco2, GEO, SW480, SW48, Lovo and SW620 human colon carcinoma cell lines. Correlations with pathological characteristics of the specimens were analysed with chi-square test. To verify the functional status of CXCR4, cell lines were tested in adhesion, migration, and proliferation assays.


RESULTS
We studied the expression of CXCR4 in 88 human colorectal tissues and we found that CXCR4 was expressed in > 10% of epithelial cells in 50% of normal mucosae (7/14), in 55% of polyps (29/53), in all of carcinomas (16/16) and hepatic metastasis (5/5). Notably, CXCR4 was significantly over-expressed in cancerous lesions (carcinomas and metastasis) compared to non-cancerous lesions (normal mucosa and polyps) (P = 0.003) and in adenomatous polyps versus hyperplastic polyps (P = 0.009). The diameter of a polyp was also significantly associated with CXCR4 expression (P = 0.031). SW480, SW48 and SW620 cell lines showed the highest levels of CXCR4 (60-80% of positive cells). Adhesion, migration, and proliferation increased in response to the CXCL12 chemokine. These effects were abrogated by the addition of anti-CXCR4 antibodies. Further, CXCL12 activated ERK1/2 in SW480 cells.


CONCLUSIONS
These data suggest that CXCR4 might play a role in colon cancer cell properties and that anti-CXCR4 antibodies could have therapeutic effects against colorectal cancer.
Ottaiano
Alessandro
A
Division of Clinical Immunology, National Cancer Institute, via M. Semmola, 80131 Naples, Italy. ale.otto@libero.it
di Palma
Antonella
A
Napolitano
Maria
M
Pisano
Carmen
C
Pignata
Sandro
S
Tatangelo
Fabiana
F
Botti
Gerardo
G
Acquaviva
Angela Maria
AM
Castello
Giuseppe
G
Ascierto
Paolo Antonio
PA
Iaffaioli
Rosario Vincenzo
RV
Scala
Stefania
S
D000906:Antibodies / Q000276:immunology; D018938:Caco-2 Cells; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002633:Chemotaxis / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D009362:Neoplasm Metastasis / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000276:immunology*
D000906:Antibodies; D019718:Receptors, CXCR4