Lymphatic or Hematogenous Dissemination: How Does a Metastatic Tumor Cell Decide?

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Lymphatic or Hematogenous Dissemination: How Does a Metastatic Tumor Cell Decide?


Abstract-

The formation of distant metastases is the deadliest phase of cancer progression. Although numerous studies have identified genes and mechanisms that affect metastasis after tumors have reached secondary sites, our knowledge about how cancer cells initially gain access to systemic circulation is limited. Since tumors can enter the blood directly by intravasating into venous capillaries or indirectly via lymphatics, it is important to evaluate the relative contributions of both pathways as routes of egress from the primary site. Insights into tumor and stromal factors governing the intravasation process may help explain why certain tumors exhibit “preferred” pathways for metastatic dissemination, both clinically and in experimental animal models.

Under lymphatic or blood dessimination-

Metastatic bias is illustrated by the fact that carcinomas and melanomas tend to develop lymph node metastases more frequently than sarcomas,14 although it is unclear whether this disparity is due to differences in intravasation and/or growth. Lymph nodes are often the first site of metastasis in a variety of cancers, and are critical for tumor staging and prognosis.22 In prostate cancer, for instance, 75% of patients bearing lymph node metastases at the time of diagnosis will possess bone metastases within 5 years, regardless of treatment.23 The presence of tumor cells in the bone-marrow is also predictive of distant metastases in a variety of tumors, particularly carcinomas.20 On the other hand, the prognostic value of circulating tumor cells in the blood is debated, as current techniques for detection suffer from problems such as low sensitivity and high rates of false positives.24,25 However, recent studies using an automated platform for detecting tumor cells in the blood, called CellSearch, have reported significant correlations between the presence of circulating tumor cells and poor clinical outcome for breast cancer patients

Conclusion-

A confluence of factors likely influences whether primary tumors metastasize via blood vessel or lymphatic routes and, related to that, how tumor cells reach the systemic circulation. Differentiation programs innate to the cell of origin of each tumor may predetermine the metastatic phenotype, though additional genetic or epigenetic changes may also affect a cell’s ability to intravasate. Morphological differences between blood vessels and lymphatics will almost certainly affect the initial route of spread, and in this regard, peritumoral lymphatics might be considered a default pathway for tumors incapable of crossing blood endothelial boundaries. However, active mechanisms for attracting tumor cells towards one type of vasculature versus another cannot be discounted. In addition, the roles played by inflammatory77 and host hematopoietic precursor cells78 in affecting the process will need to be further examined.

At the same time, improved imaging techniques should allow simultaneous visualization of blood vessel and lymphatic intravasation within the same tumor, allowing direct measurements of the relative frequencies of each occurrence. In addition, genomic approaches combined with clustering algorithms should be able to elucidate molecular relationships between disseminated tumor cells and cells derived from the primary tumor and/or lymph node metastases. These studies will likely yield detailed information about how and when metastatic cells leave the primary tumor. Lastly, identification and validation of genes and proteins that affect the intravasation process and perhaps specify whether a tumor invades via blood vessel or lymphatic routes, as has been recently proposed,79 will have valuable clinical implications for prognosis and treatment.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459485/