Brief Article
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World J Gastroenterol. Nov 21, 2013; 19(43): 7788-7794
Published online Nov 21, 2013. doi: 10.3748/wjg.v19.i43.7788
Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer
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
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
Author contributions: Li ZJ and Ying XJ designed the research and wrote the manuscript; Chen HL, Ye PJ, Li G and Jiang HF performed the experiments; Liu J and Zhou SZ performed the statistical analysis; Liu J and Chen ZL collected the clinical data and provided some useful comments during the study; all authors have read and approved the final manuscript.
Supported by Technological Research Project for Public Welfare from Science and Technology Department of Zhejiang Province, No. 2010C33099
Correspondence to: Xiao-Jiang Ying, MD, Department of Colorectal Surgery, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, No. 568, Zhongxing North Street, Shaoxing 312000, Zhejiang Province, China. lzdx2003@163.com
Telephone: +86-575-88229151 Fax: +86-575-88228823
Received: July 24, 2013
Revised: September 18, 2013
Accepted: September 29, 2013
Published online: November 21, 2013
Processing time: 146 Days and 13.2 Hours
Abstract

AIM: 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.

CONCLUSION: IGF-1/IGF-1R signaling induces tumor-associated lymphangiogenesis and contributes to lymphatic metastasis of CRC.

Keywords: Colorectal cancer; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor; Lymphangiogenesis; Lymphatic metastasis

Core tip: Insulin-like growth factor-1 (IGF-1) and its receptor, insulin-like growth factor-1 receptor (IGF-1R), are frequently overexpressed in many types of tumors including colorectal cancer. A recent study (Björndahl et al, 2003) showed that both IGF-1 and IGF-2 could potently stimulate lymphatic vessel growth in the mouse cornea. However, equivalent evidence on IGF-1 in solid tumors is lacking. Here, we show that IGF-1/IGF-1R signaling induces tumor-associated lymphangiogenesis in vivo and contributes to lymphatic metastasis of colorectal cancer. Findings from the present study provide further evidence to support the involvement of IGF-1/IGF-1R signaling in lymphangiogenesis in solid tumors.