Paraneoplastic syndromes: mechanisms.

Neoplasms may affect distant host tissues, but they always involve normal physiologic mechanisms. Van R. Potter said that "Oncogeny is blocked ontogeny," so tumors are committed to their organ anlagen. Paraneoplastic mediators are appropriate to their blocked anlagen stages. Mediators may have autocrine, paracrine, or endocrine actions. However, their release and distribution depend on the mode of cell death, and the spatial relations to host vascularity. Invasiveness and metastasis are means of normal embryonic development, and not new cancer-specific properties. Nor do human cancers acquire new foreign genetic information; thus, they cannot express neoantigens nor be recognized by the host. However, tumors breach the blood-brain barrier and basement membrane separations of ectoderm from mesenchyme and release "forbidden" self-antigens, to which host immunocytes may respond causing cell- and antibody-mediated autoimmunity. This can damage normal host tissues by a "bystander" effect. Paraneoplastic mechanisms can also be analyzed as arising from three-way interactions between cells blocked in ontogeny, their molecular messengers, and the host tissues they target.