Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify novel, tissue-restricted cell surface proteins in cancer which can serve as targets for antibody-based diagnostics and therapeutics, a translated version of the expressed sequence tag database (tblastn) was mined for transcripts with similarity to the glycoprotein A33 (GPA33) colon cancer antigen. A novel human transcript, termed A34, was identified which encoded a putative cell surface protein, GPA34, which is approximately 30% identical to GPA33 and other members of the junctional adhesion molecule (JAM) family. Conventional end-point and quantitative real-time RT-PCR showed that A34 mRNA expression is highly tissue-restricted, as it is expressed predominantly in stomach and testis. A34 mRNA was also detected in 6/19 (31%) gastric cancers, 8/16 (50%) esophageal carcinomas, and 4/17 (23%) ovarian cancers, but not in lung, breast or colon carcinomas. A murine monoclonal antibody (mAb A34) was generated to the extracellular domain of the A34 protein and used to biochemically and immunohistochemically characterize the A34 antigenic system. The mAb A34 specifically recognized glycoproteins ranging in apparent size from 55-70 kDa, present in normal gastric mucosa and in COS-7 cells transfected with A34 cDNA. Of 31 different normal tissues examined by immunohistochemistry, GPA34 protein expression was detected primarily in normal stomach mucosa and testicular germ cells, and in the tumor cells of 5/17 (29%) gastric cancers, 7/11 (63%) esophageal cancers, and 2/21 (9%) ovarian cancers, in agreement with gene expression results. The A34 antigen and monoclonal antibody may be of considerable value for immunotherapy of different types of cancer.
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PMID:Glycoprotein A34, a novel target for antibody-based cancer immunotherapy. 1640 1

How cells with metastatic potential, or pro-metastatic states, arise within heterogeneous primary tumors remains unclear. Here, we have used one index primary colon cancer to develop spiked-scRNAseq to link omics-defined single-cell clusters with cell behavior. Using spiked-scRNAseq we uncover cell populations with differential metastatic potential in which pro-metastatic states are correlated with the expression of signaling and vesicle-trafficking genes. Analyzing such heterogeneity, we define an anti-metastatic, non-cell-autonomous interaction originating from non-/low-metastatic cells, and identify membrane VSIG1 as a critical mediator of this interaction. VSIG1 acts to restrict the development of pro-metastatic states autonomously and non-cell autonomously, in part by inhibiting YAP/TAZ-TEAD signaling. As VSIG1 re-expression is able to reduce metastatic behavior from multiple colon cancer cell types, the regulation of VSIG1 or its effectors opens new interventional opportunities. In general, we propose that crosstalk between cancer cells, including the action of VSIG1, dynamically defines the degree of pro-metastatic intra-tumoral heterogeneity.
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PMID:Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1. 3317 37