Significance and Mechanism of Lymph Node Metastasis in Cancer Progression

Abstract

The effect of local therapy, such as surgical lymph node (LN) dissection and radiotherapy, on the survival of cancer patients has been debated for decades. Several lines of recent clinical evidence support that LN metastasis plays significant roles in systemic dissemination of cancer cells, although the effects of surgical LN dissection on survival was downplayed historically because of controversial data. Molecular studies of LN metastasis suggest that the microenvironment within LNs, including chemokines and lymphangiogenesis, can mediate the metastatic spread to the sentinel LNs, and beyond. It has been shown that chemokine receptor CXCR3 is involved in LN metastasis, and its inhibition may improve patient prognosis. Although it remains to be determined whether local therapy is best pursued through LN dissection or through a combination of resection with radiation, prevention of regional metastases is an important goal in the treatment of cancer patients to achieve a better survival. Cancer Res; 71(4); 1214-8. Ó2011 AACR.

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

“…[6][7][8][9][13][14][15] In CRC, it was reported that CXCR3 expression is upregulated in metastatic colon cancer cells, but not in their primary lesions, and that the CXCL10/CXCR3 axis…”

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

“…2,37,44 However, tumors may manipulate the LN microenvironment to provide hospitable soil for the seeding and proliferation of tumor cells. 12 In the current study, we observed that levels of CD169 C CD8 C T cells were significantly lower in peri-LN than distant-LN, and the ratios of CD169 C CD8 C T cells in both peri-LN and distant-LN were higher in early stage CRC patients than those in advanced stages.…”

“…Additionally, tumors have been suggested to significantly modulate the microenvironment of LNs. 37,38,40 Thus, a better understanding of the mechanism of tumor-modulating CD169 C CD8 C T cells may be used to develop new cancer immunotherapies.…”

Expression of CXCR-4 and IDO in human colorectal cancer: An immunohistochemical approach

“…Chemokinetic functions in the immune system, chemokines and their receptors also exert critical roles in tumor initiation, progression and metastasis (6). CRC cells have been shown to express the chemokine receptors, CXCR4 and CXCR3 (7)(8)(9)(10)(11)(12). In a clinical study, CXCR4 expression in CRC was revealed to increase the recurrence of the cancer, poor survival and liver metastasis (8).…”