BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) a...BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) and integrin-β1(ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation(EMT) and lead to metastasis.AIM To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche.METHODS The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase(FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1(SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue.RESULTS The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1β, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche.CONCLUSION Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.展开更多
BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimet...BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.展开更多
基金Supported by the National Natural Science Foundation of China,No.81673944
文摘BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) and integrin-β1(ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation(EMT) and lead to metastasis.AIM To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche.METHODS The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase(FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1(SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue.RESULTS The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1β, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche.CONCLUSION Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.
基金by National Natural Science Foundation of China,No.81673944.
文摘BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.
