Table 1.

Molecules potentially involved in tumor cells trafficking through the lymphatic vessels.

Molecule involved in cell migration	Role in leucocytes trafficking by lymphatic vessels	Expression on tumor cells	Influence on tumor progression
CCR7	Upregulated CCR7 during activation and maturation of DCs to respond to lymphatic-secreted CCL21 and elicits directional migration62	Melanoma, colorectal, mammary, gastric, non-small cell lung, head and neck cancers, thyroid and squama cell carcinomas42,63	Expression is correlated with lymph node metastasis.
CCR4	Selectively expressed on Th2 cells and regulatory T cells	Breast, lung, gastric cancer 64	Expression is associated with lung and lymph nodes metastasis. In breast cancer, correlated with HER2 positive tumors and poor prognosis
ICAM-1	ICAM-1 knockout mice have defects in lymph node recruitment of DCs43	Melanoma, breast cancer, gastric cancer, esophageal cancer, colorectal carcinoma65	The results are controversial. In some cases ICAM-1 plays a major role in invasion of cancerous cells while in others decreased expression inhibits formation of metastases66
COX-2	COX-2 plays an important role in leucocytes migration and adhesion, likely by modulating p110g PI3K–mediated cell signaling67	Breast cancer, esophageal cancer pancreatic cancer, various colorectal tumors, adenocarcinoma, prostate and bladder cancers68	Upregulates CCR7 via EP2/EP4 receptor signaling pathways and enhances lymphatic metastasis
CD99	Involved in transmigration of monocytes, neutrophils, lymphocytes and DCs	Ewing sarcoma, synovial sarcoma and low-grade fibromyxoid sarcoma69	Knocking down CD99 in Ewing sarcoma reduces tumor ability to form metastases