To analyze unique molecular differences between normal and neoplastic cells, we have examined host responses to
tumor cells. The present study provides the first evidence for an innate rapid recognitive response of the lymphoid system to some syngeneic
tumors. The lymphoid procoagulant (PCA) response, a T cell-instructed monocyte response that activates
proteases of the coagulation cascade culminating in
thrombin formation, is considered a component of classic delayed-type
hypersensitivity responses. We have demonstrated that three syngeneic rat mammary
carcinomas elicit this cellular response in vitro in lymphoid cells of the unimmunized rat. The response was rapid, reaching maximum within 6 hr. Analysis was compounded by the constitutive PCA activity of some
tumors; however, the PCA product produced in the response to
tumor challenge in vitro was newly biosynthesized and was of lymphoid cell origin, differing from the PCA of
tumor cells. The lymphoid PCA response was
prothrombinase-like and did not require
vitamin K for biosynthesis, nor were other gamma-carboxylation-dependent extrinsic pathway
proteases other than
prothrombin required for
thrombin generation. Both in vivo and in vitro derived mammary
carcinoma cells elicited the response, whereas a
fibrosarcoma and nontransformed syngeneic cells did not.
Tumor shed substances, which were devoid of PCA and sedimentable only in part at 100,000 X G, induced this cellular response. The same stimuli shed from
tumor cells did not directly elicit a PCA response from elicited peritoneal macrophages; however, in the presence of T lymphocytes a PCA response of these macrophages was produced. This study provides novel information to indicate that a T-enriched lymphocyte-dependent monocyte-macrophage response to some
tumors, before effective in vivo immunization, may participate in initial local
protease generation and
fibrin deposition, both thought to play a significant role in the local pathobiology of
tumors.