title: In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma.
abstract: Basal cell carcinoma (BCC) is characterized by slow growth, virtual absence of metastases, and strong stroma-dependency. Cancer-associated fibroblasts (CAFs) in the tumor stroma influence tumor growth, invasion, and metastasis. To comprehensively characterize CAFs of BCC in their in situ cancer environment, laser capture microdissection, linear gene amplification, microarray analysis, and quantitative real-time PCR (qRT-PCR) were combined. Pair-wise comparison of gene expression of microdissected CAFs and corresponding normal perifollicular fibroblasts identified 65 genes that were significantly upregulated in at least two of three different patients. Among the annotated genes, as many as 13 genes encoded secreted proteins, of which six were previously implicated as CAF-associated proteins in various tumor types. Four of the seven novel CAF genes--matrix Gla-protein, secreted frizzled-related protein 2, angiopoietin-related protein-2, and platelet-derived growth factor receptor-like protein--were selected for further analyses by qRT-PCR and were found to be frequently upregulated in CAFs of three independent BCC tissues. Analyses of CAFs from squamous cell cancer, prostate cancer, and colon cancer did not indicate that these genes were upregulated in these cancers. This study thus validates a novel approach for comprehensive characterization CAFs in their in situ environment of BCC. The results suggest a specific expression profile of CAFs in BCC possibly accounting for disease-specific pathological roles.
authors.affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Kai
authors.initials: K
authors.lastname: Kappert
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohshima
authors.forename: Christina
authors.initials: C
authors.lastname: Sundquist
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheidl
authors.forename: Per
authors.initials: P
authors.lastname: Lindahl
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Heldin
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.forename: Arne
authors.initials: A
authors.lastname: Ostman
mesh_terms: D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042282:Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology