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PECAM‐1 and Tumor Metastasis
Author(s) -
DeLisser Horace Michael,
Cao Gaoyuan,
Fehrenbach Melane,
Desprez Pierre,
Liu Yong,
Liggitt Denny,
Thor Ann,
Debs Robert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a78-a
Subject(s) - angiogenesis , lewis lung carcinoma , metastasis , cancer research , null cell , melanoma , biology , apoptosis , pathology , medicine , immunology , cancer , cell culture , biochemistry , genetics
PECAM‐1, a vascular cell adhesion molecule on leukocytes and endothelial cells (EC), has been implicated in leukocyte recruitment and angiogenesis. It has also been suggested to play a role in tumor metastasis, but its involvement in this process is unclear. Studies were therefore done of the effects of anti‐PECAM‐1 antibody (mAb 390) treatment on the growth of tumors in murine lung following tail vein tumor cell injection. The following tumors were studied: B16 melanoma, 4T1 mammary carcinoma, CT26 colon carcinoma and human LOX melanoma. mAb 390 treatment (5–6 doses) started 7 days after tumor injection inhibited the development of tumor deposits in the lung. This inhibition was not associated with reduced vessel density, inflammatory cell infiltration or tumor apoptosis, necrosis or infarction. The development of lung metastases was also noted to be inhibited in PECAM‐1‐null mice. Further, reconstitution of PECAM‐1‐null animals with wild type marrow did not restore the wild type phenotype while transplantation of PECAM‐1‐null marrow into wild type mice did not confer the null phenotype. These data suggest that the inhibition produced by mAb 390, as well as that observed in PECAM‐1‐null mice are mediated by the loss of functional PECAM‐1 on vascular EC and provide evidence of a possible role for endothelial PECAM‐1 in tumor metastases to the lung. Supported by the DOD ( PR043482 ), NIH ( HL079090 ) & Genomic Systems.