Gene expression profiling identifies matriptase overexpression in malignant mesothelioma.
OBJECTIVE
We investigated the gene expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel genes that are potentially involved in the oncogenic transformation of human pleural cells.


METHODS
Complementary DNA (cDNA) microarray transcriptional profiling studies of 10 MPM cell lines and 4 MPM primary tumor specimens were performed using hierarchic clustering. To confirm microarray data, we used real-time polymerase chain reaction and immunoblotting.


RESULTS
Cluster analysis differentiated among epithelial (E), sarcomatoid, and biphasic MPM variants. Expression profiling identified common overexpressed or underexpressed genes in MPM. Notably, matriptase messenger RNA was found to be overexpressed by 826-fold in E MPM, with protein expression subsequently confirmed by immunoblot analysis. This recently characterized trypsin-like serine protease has been implicated in tumor invasion and metastasis of E-derived cancers, but has not been described until now in MPM. We also identified other novel genes, such as insulin-like growth factor binding protein 5 and a cDNA clone similar to proteolipid MAL2.


CONCLUSIONS
Thus, further large-scale profiling of MPM may elucidate previously unrecognized molecular mechanisms by identifying novel genes that are involved in malignant transformation. Our study has now found matriptase to be one of these mesothelioma-associated genes, with potential pathogenic and therapeutic significance.
Hoang
Chuong D
CD
Department of Surgery, Division of Cardiovascular and Thoracic Surgery, University of Minnesota Medical School, Minneapolis, MN, USA.
D'Cunha
Jonathan
J
Kratzke
Marian G
MG
Casmey
Carrie E
CE
Frizelle
Sandra P
SP
Maddaus
Michael A
MA
Kratzke
Robert A
RA
D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008654:Mesothelioma / Q000201:enzymology* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000201:enzymology* / Q000235:genetics*; D012697:Serine Endopeptidases / Q000096:biosynthesis*
D012697:Serine Endopeptidases; C485595:matriptase; C485596:ST14 protein, human