HGF and ligation of alphavbeta5 integrin induce a novel, cancer cell-specific gene expression required for cell scattering.
Hepatocyte growth factor (HGF), a cytokine involved in tumorigenesis and most metastases, initiates cell migration by binding to the protooncogene c-Met receptor. In epithelial carcinoma cells, c-Met activation causes the breakdown of E-cadherin cell-cell contacts leading to cell spreading. While the breakdown of E-cadherin contacts is immediate, HGF-induced migration requires transcription. To test the hypothesis that this de novo mRNA synthesis includes cancer cell-specific transcripts, we performed subtraction hybridization to isolate HGF-induced transcripts from an endometrial epithelial carcinoma cell line, RL95-2 (RL95), known to migrate but not to proliferate with HGF treatment. One novel cDNA we call Mig-7 is induced by HGF in endometrial epithelial carcinoma cell lines RL95 and HEC-1A before migration ensues. Ovarian, oral squamous cell, and colon metastatic tumors but not normal tissues express Mig-7. HGF did not induce Mig-7 in normal primary endometrial epithelial cells. In addition, blocking antibodies to alphavbeta5 integrin inhibited HGF induction of Mig-7 in RL95 cells. Most importantly, Mig-7-specific antisense oligonucleotides inhibited scattering of RL95 cells in vitro. These results are the first to demonstrate that Mig-7 expression may be used as a cancer cell-specific target to inhibit cell scattering.
Crouch
Sonya
S
Pharmaceutical Sciences Department, Texas Tech University Health Science Center School of Pharmacy, Amarillo, TX 79106, USA.
Spidel
Celee S
CS
Lindsey
J Suzanne
JS
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence / Q000235:genetics; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence / Q000235:genetics; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000302:isolation & purification; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000302:isolation & purification; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D000906:Antibodies; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D016023:Integrins; D009363:Neoplasm Proteins; D020320:Oligoribonucleotides, Antisense; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; C482285:TOX4 protein, human; C064660:integrin alphaVbeta5; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met