2Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, ul. Savinykh 12/1, 634028 Tomsk, Russia
3Siberian State Medical University, Moskovskii Trakt 2, 654050 Tomsk, Russia; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received September 12, 2012; Revision received November 11, 2012
The formation of lymphogenic metastases remains enigmatic. In particular, the much more pronounced predilection of carcinomas than of sarcomas to metastasizing into regional lymph nodes is an unsolved problem. We suggest that this difference could be due to the ability of epitheliocytes for a hypothetical process termed by us “collateral presentation of antigens”. Under conditions of infection of epithelium with intracellular pathogens or during inflammation, epithelial cells acquire a special receptor phenotype, undergo the epithelial–mesenchymal transition, and migrate along lymphatic vessels into lymph nodes where they present antigen to immunocytes. The collateral presentation of antigens can be of significant biological importance in the case of insufficient classical pathway of antigen presentation (by dendritic cells) or on disturbance in the death mechanisms of the infected cells. Depending on conditions of induction of the epithelial–mesenchymal transition and on possible ability of epitheliocytes to express MHC II with co-stimulating molecules, two pathways, “container-mediated” and “MHC II-dependent”, of antigen presentation in lymph nodes resulting in development of immunogenesis or anergy of immunocytes are supposed to exist. All pathways of delivery of the epithelial cells into lymph nodes and of antigen presentation by epitheliocytes terminate by death of these cells. The lymphogenic metastasizing realizes the same mechanism under conditions of tumor disease; however, this is not associated with cell death, but they actively colonize the lymph node. The proposed hypothesis allows us to explain the metastasizing of sarcomas into lymph nodes. The main prerequisite for lymphogenic metastasizing seems to be related with the mesenchymal–epithelial transition of sarcoma cells promoting their involvement in the presentation of antigens.
KEY WORDS: collateral presentation of antigens, lymphogenic metastasizing, benign epithelial inclusions, MHC II, carcinomas, sarcomas