Significance and mechanism of lymph node metastasis in cancer progression.

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.