CXCL10 promotes invasion-related properties in human colorectal carcinoma cells

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2007-04, Vol.67 (7), p.3396-3405
Main Authors: ZIPIN-ROITMAN, Adi, MESHEL, Tsipi, SAGI-ASSIF, Orit, SHALMON, Bruria, AVIVI, Camila, PFEFFER, Raphael M, WITZ, Isaac P, BEN-BARUCH, Adit
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Biopsy
Cell Line, Tumor
Cell Transformation, Neoplastic - metabolism
Chemokine CXCL10
Chemokines, CXC - biosynthesis
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Interferon-gamma
Liver Neoplasms - metabolism
Liver Neoplasms - secondary
Lung Neoplasms - metabolism
Lung Neoplasms - secondary
Lymphatic Metastasis
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Pharmacology. Drug treatments
Protein Isoforms
Receptors, Chemokine - biosynthesis
Receptors, CXCR3
Signal Transduction
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-06-3087