title: Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7.
abstract: The precise mechanisms governing invasion at the leading edge of squamous cell carcinoma (SCC) and its subsequent metastasis are not fully understood. We aimed to define the cancer-related molecular changes that distinguish noninvasive tumor from invasive SCC. To this end, we combined laser capture microdissection with complementary DNA (cDNA) microarray analysis. We defined invasion-associated genes as those differentially regulated only in invasive SCC nests, but not in actinic keratosis or in situ SCC, compared with normal epidermis. There were 383 upregulated and 354 downregulated genes in the "invasion set." SCC invasion was characterized by aberrant expression of various proteolytic molecules. We noted increased expression of MMP7 and IL-24 in invasive SCC. IL-24 induced the expression of matrix metallopeptidase 7 (MMP7) in SCC cells in culture. In addition, blocking of MMP7 by a specific antibody significantly delayed the migration of SCC cells in culture. These results suggest a possible contribution of IL-24 to SCC invasion via enhancing focal expression of MMP7, although IL-24 has been suggested to have antitumor growth effects in other cancer types. Identification of regional molecular changes that regulate cancer invasion may facilitate the development of new targeted treatments for aggressive cancer.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; Center for Clinical and Translational Science, The Rockefeller University, New York, New York, USA.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Texas Dermatology Associates, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Kejal R
authors.initials: KR
authors.lastname: Shah
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA; Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Cannizzaro
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: Israel
authors.initials: I
authors.lastname: Coats
authors.affiliation: Institute for Pediatric Urology, Department of Urology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Felsen
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center, New York, New York, USA. Electronic address: john.carucci@nyumc.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Carucci
mesh_terms: D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D020783:Matrix Metalloproteinase 7; D000099180:Interleukin-24; C060932:MMP7 protein, human