Expression of the FAP gene in non-fibroblast human cell lines. Development of cancer-associated fibroblast models

Abstract

The fibroblast activation protein (FAP) is selectively expressed in cancer-associated fibroblasts (CAFs) and facilitates tumor progression, which makes this protein an attractive therapeutic target. There are difficulties in obtaining CAFs for studying the function and suppression of FAP. In this work, the expression level of FAP was determined by PCR assay in 25 human cell lines and 8 surgical samples of tumor stroma. The expression of FAP was observed in all tumor stroma samples and in four cell lines: NGP-127, SJCRH30, SJSA-1, and A375. The level of FAP expression in NGP-127, SJCRH30, and SJSA-1 lines as well as in CAFs of patients was comparable, which makes these cell lines a possible model for studying FAP.

BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins

“…Immunohistochemistry (IHC) of BCL9 and FAP (used as a C1featured probe and marker of stromal cell infiltration) 25 on a tissue microarray (TMA) of CRC samples (n = 89) revealed that stromal and ganglion cells have the highest level of BCL9 staining in normal colon mucosa ( Supplementary Fig. 3a).…”

Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics

“…FAP expression is typically low to undetectable in most normal adult tissues, but is highly upregulated in a multitude of cancers, including almost all carcinomas. In tumors, various mesenchymal cells express FAP, including mesenchymal stem cells (MSCs), CAFs, sarcoma, and melanoma cells( 15 – 18 ). FAP expression on epithelial tumor cells has also been reported, but the prevalence and significance of this remains to be established.…”

“…Yet even when these tissues do not show histological evidence of tumor cells, the presence of tumor elsewhere in the same organ can have effects on distal tissue, and thus classifying these samples as “normal” is often misleading. In human tumor-adjacent tissues, FAP was detectable at the RNA level by RT-PCR in the context of esophageal squamous cell carcinoma (ESCC)( 19 ), lung carcinoma( 18 ), and glioma( 17 ). At the protein level, FAP was found in pancreatic ductal adenocarcinoma (PDAC) adjacent tissue( 20 , 21 ).…”

Copy Number Alterations in Hepatoblastoma: Literature Review and a Brazilian Cohort Analysis Highlight New Biological Pathways

“…We could restrict the minimum amplified region to a 5.3 Mb segment at 2q24.2q24.3, harboring 33 genes; however, the smallest 2q24 amplified region identified in HBs was documented by Kato et al ( 30 ) a ~2 Mb region (chr2: 162954232-164891865; hg19), fully contained in our delimited region, and encompassing only eight genes ( LOC101929532 , GCG , FAP , IFIH1 , GCA , KCNH7 , KCNH7-AS1 , FIGN ). Two genes mapped on the larger 5.3 Mb amplification region could be highlighted: FAP , expressed mainly during embryogenesis, and in cancer-associated fibroblasts ( 33 ), and DPP4 , which is overexpressed in several tumors and described as having a pro-oncogenic role in hepatocellular carcinoma ( 34 ). We have previously profiled the mRNA expression of 48 genes mapped to a 10 Mb 2q24 amplification ( 12 ), a larger segment encompassing ours and the smallest 2q24 amplified region documented by Kato et al ( 30 ); only five genes were found to be significantly upregulated in the investigated tumors ( DAPL1, ERMN, GALNT5, SCN1A and SCN3A ).…”