Defective tumor vascularization induced by metastasin 1 expression.
It has been proposed that metastasin 1 (mts1), a member of the S100 Ca(2+)-binding protein family, may play a role in tumor progression and metastasis. In order to test this possibility, we have performed gene transfer experiments using a human sense mts1 expression vector and human MCF7 malignant epithelial cells which do not express endogenous mts1. In vitro, mts1 expression did not modify proliferative or invasive properties of transfected MCF7 cells. In vivo, MCF7 cells expressing mts1 were associated with tumors exhibiting necrosis, and abundant fibrous and poorly cellular stroma. Immunohistochemical staining of endothelial cells showed that, in the presence of mts1, the number and the size of tumoral microvessels were decreased and some of them were collapsed. No metastases were observed in mice with either mts1-expressing or nonexpressing tumors. In summary, these results indicate that (i) in vitro and in vivo, mts1 does not confer invasive properties to MCF7 cells, and (ii) mts1 expression by MCF7 cells leads to defective tumor microvessels, leading to the hypothesis that mts1 may have a negative effect on neoangiogenesis and/or on the maintenance of blood vessels.
Onischenko
A
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, Illkirch, France.
Chenard
M P
MP
Lefebvre
O
O
Bruyneel
E
E
Rio
M C
MC
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology
D002135:Calcium-Binding Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C077591:S100A4 protein, human