Inhibition of tumor growth and metastatic spreading by overexpression of inter-alpha-trypsin inhibitor family chains.
The inter-alpha trypsin inhibitor (ITI) family is a group of proteins built up from different combinations of I light chain (ITI-L) and 3 highly homologous heavy chains (ITI-HI, -H2 and -H3). To investigate a potential role of the ITI family chains in cancer and metastasis spreading, we engineered human H460M cell lines expressing both the green fluorescent protein (GFP) and one of these chains. These clones were subcutaneously injected in athymic nude mice, and lung metastasis number and primary tumor weight were determined after 28 days. Expression of the ITI-L chain considerably decreased tumor weight and fluorescent lung metastasis number. ITI-HI and ITI-H3 chain expression induced a significant decrease of metastasis number, whereas no decrease of tumor weight could be detected. In vitro, ITI-L expression significantly decreased chemotaxis and ITI-HI and ITI-H3 expression increased cell attachment. These results argue for the antitumoral or antimetastatic properties of ITI-L, -HI and -H3 chains.
Paris
Sébastien
S
Sesboüé
Richard
R
Delpech
Bertrand
B
Chauzy
Claude
C
Thiberville
Luc
L
Martin
Jean-Pierre
JP
Frébourg
Thierry
T
Diarra-Mehrpour
Maryam
M
D000510:Alpha-Globulins / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D005434:Flow Cytometry; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D021122:Protein Subunits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014361:Trypsin Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000510:Alpha-Globulins; D008164:Luminescent Proteins; D011498:Protein Precursors; D021122:Protein Subunits; D014361:Trypsin Inhibitors; C061151:pre-alpha-trypsin inhibitor; D049452:Green Fluorescent Proteins; C011877:inter-alpha-inhibitor