title: CXCL10 promotes invasion-related properties in human colorectal carcinoma cells.
abstract: CXCL10 was recently shown to exert antimalignancy functions by influencing the tumor microenvironment. Here, we have taken a different approach, investigating the effects of CXCL10 directly on tumor-promoting functions in colorectal carcinoma (CRC) cells. CXCL10 expression was detected in preferred metastatic sites of CRC (liver, lungs, and lymph nodes), and its CXCR3 receptor was expressed by eight CRC cell lines (detected: reverse transcription-PCR and/or flow cytometry). Detailed analysis was done on two cell lines derived from primary CRC tumors (SW480, KM12C) and their metastatic descendents (SW620 and KM12SM). The three known variants of CXCR3 (CXCR3-A, CXCR3-B, and CXCR3-alt) were detected in all four cell lines. CXCR3 expression was also observed on colorectal tumor cells in biopsies of CRC patients (immunohistochemistry). CXCL10 and CXCR3 expression were potently induced in CRC cells by Interferon gamma and all four CRC cell lines responded to CXCL10 by extracellular signal-regulated kinase 1/2 dephosphorylation. The chemokine did not affect tumor cell growth or angiogenesis-related functions in the tumor cells, such as CXCL8 and vascular endothelial growth factor secretion. Importantly, CXCL10 significantly up-regulated invasion-related properties in CRC cells: It promoted matrix metalloproteinase 9 expression and induced CRC cell migration. Of note, CXCL10-induced migration was detected only in the two metastatic cells and not in their primary counterparts. Also, CXCL10 promoted the adhesion of metastatic cells to laminin. These results suggest that CXCL10 can be exploited by CRC cells toward their progression, thus possibly antagonizing the antimalignancy effects of the chemokine on the tumor microenvironment. Therefore, care should be taken when considering CXCL10 as a therapeutic antitumor modality for CRC treatment.
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Zipin-Roitman
authors.forename: Tsipi
authors.initials: T
authors.lastname: Meshel
authors.forename: Orit
authors.initials: O
authors.lastname: Sagi-Assif
authors.forename: Bruria
authors.initials: B
authors.lastname: Shalmon
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.forename: Raphael M
authors.initials: RM
authors.lastname: Pfeffer
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Witz
authors.forename: Adit
authors.initials: A
authors.lastname: Ben-Baruch
mesh_terms: D000818:Animals; D001706:Biopsy; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D015398:Signal Transduction
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D020033:Protein Isoforms; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma