Abstract
Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates both in tumor stroma and cancer cells and is highly regulated by various cytokines. The aberrant expression of versican and its isoforms is known to modulate cell proliferation, differentiation, and migration, all of which are features of the invasion and metastasis of cancer; versican is also known to favour the homeostasis of the ECM. Interleukin-11 (IL-11) is an important cytokine that exhibits a wide variety of biological effects in gastric cancer development. Here, we analysed the expression of versican isoforms and found that the major isoforms expressed by both gastric carcinoma tissue and gastric cell lines were V0 and V1, and V1 was significantly higher in gastric carcinoma tissue. The treatment of the gastric cell lines AGS and MKN45 with rhIL-11 resulted in a significant increase in the expression of V0 and V1. Exogenous IL-11 increased migration in AGS and MKN45 cells, whereas these effects were reversed when the expression of V0 and V1 were abolished by siRNA targeting versican V0/V1. Collectively, these findings suggest that the abnormally expressed versican and its isoforms participate, at least in part, in the progress of gastric carcinoma triggered by IL-11.
Keywords:
IL-11; Versican; gastric carcinoma; migration..
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Aged
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Cell Division / drug effects
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / metabolism
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Cell Movement / drug effects
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Disease Progression
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Extracellular Matrix / physiology
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Female
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Gastric Mucosa / metabolism
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Interleukin-11 / pharmacology*
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Interleukin-11 / physiology
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Male
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Middle Aged
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Protein Isoforms / biosynthesis
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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RNA Interference
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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RNA, Small Interfering / pharmacology
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Stomach / cytology
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Stomach Neoplasms / genetics*
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology
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Versicans / antagonists & inhibitors
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Versicans / biosynthesis
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Versicans / chemistry
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Versicans / genetics
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Versicans / physiology*
Substances
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IL11 protein, human
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Interleukin-11
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Neoplasm Proteins
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Protein Isoforms
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RNA, Messenger
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RNA, Neoplasm
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RNA, Small Interfering
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Recombinant Proteins
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VCAN protein, human
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Versicans