Defining an invasion signature at the leading edge of cutaneous squamous cell carcinoma (SCC): IL-24 driven MMP-7 and MMP-13 expression.

ABSTRACT: Purpose: Primary cutaneous squamous cell carcinoma (SCC) can be an invasive cancer in skin and has the potential to metastasize. We aimed to define the cancer related molecular changes that distinguish non-invasive from invasive SCC. Experimental design: We used laser capture microdissection technique in combination with cDNA microarray analysis in order to determine molecular changes that associate with SCC progression. Results: We defined invasion-associated genes as those udifferentially regulated only in SCC invasive nests, but not in actinic keratosis-like dysplasia or SCC in situ regions, compared to normal epidermis. We designated these genes as “invasion signature gene set of cutaneous SCC”. Overall we found 383 up- and 354 down-regulated probe-sets that constitute the invasion signature gene set. As part of this profile, SCC invasion is associated with aberrant gene expression changes of numerous MMPs including MMP7 (FCH=5.43, FDR<0.01) and MMP13 (FCH=12.53, FDR<0.01). IL-24 is also up-regulated in the leading invasive edge of SCC (FCH=6.74, FDR<0.01). IL-24 enhanced mRNA expression of both MMP7 and MMP13 in a human SCC cell line. Laminin332, which is one of the target molecules of MMP7, had altered expression at the leading edge of SCC invasion nests at both the genomic and protein level. Conclusions: We defined the distribution of MMPs within human cutaneous SCC tissue showing distinct expression with progression from normal skin to actinic keratosis to SCC in situ to invasive carcinoma. We further suggest a potential role for IL-24 in progression to invasion via MMP7 and MMP13. Laser capture microdissection was performed on 5 cases of actinic keratosis, 5 cases of in situ SCC, and 5 cases of invasive SCC.

ORGANISM(S): Homo sapiens

SUBMITTER: Mayte Suarez-Farinas 

PROVIDER: E-GEOD-42677 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress