title: Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer.
abstract: OBJECTIVE
  To investigate the expression of insulin-like growth factor-1 (IGF-1)/insulin-like growth factor-1 receptor (IGF-1R) in colorectal cancer (CRC) tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.
  
  
  METHODS
  Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density (LVD) in 40 CRC specimens. The correlation between IGF-1/IGF-1R and LVD was investigated. Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays. A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo.
  
  
  RESULTS
  Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis (r = 0.715 and 0.569, respectively, P < 0.05) and tumor TNM stage (r = 0.731 and 0.609, P < 0.05). A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis (r = 0.405, P < 0.05). A positive correlation was found between LVD and IGF-1R expression (r = 0.437, P < 0.05). Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells. In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.
  
  
  CONCLUSIONS
  IGF-1/IGF-1R signaling induces tumor-associated lymphangiogenesis and contributes to lymphatic metastasis of CRC.
authors.affiliation: Zhen-Jun Li, Xiao-Jiang Ying, Hong-Liang Chen, Ping-Jiang Ye, Zhi-Liang Chen, Gang Li, Hua-Feng Jiang, Jiang Liu, Shu-Zhen Zhou, Department of Colorectal Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China.
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Li
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Ying
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Chen
authors.forename: Ping-Jiang
authors.initials: PJ
authors.lastname: Ye
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Hua-Feng
authors.initials: HF
authors.lastname: Jiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Colorectal cancer; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor; Lymphangiogenesis; Lymphatic metastasis