ON THE CAUSE OF THE LOCALIZATION OF SECONDARY TUMORS AT POINTS OF INJURY.
The cause of the frequent localization of secondary tumors at points of injury is not known. Our work deals with this problem. For the experiments the peritoneal cavity has been employed as offering relatively uncomplicated conditions, and the fate of mouse tumor brought into contact with a peritoneal lining injured in various ways has been studied. The injection of a suspension of mouse tumor into a healthy peritoneal cavity has little success as a rule compared with a similar injection into the subcutaneous tissue. We have found that the resistance of the peritoneal lining thus indicated can be largely if not completely abolished by the preliminary injection of a mechanical irritant (Kieselguhr, lycopodium). That the change thus brought about is independent of general immunity phenomena is shown by the fact that a local injury renders susceptible the part of the peritoneum immediately affected and that part only. Special tests show that the factor important in rendering the peritoneum more susceptible is the injury to the subendothelial connective tissue. Susceptibility persists after the endothelium has regenerated over the reacting connective tissue. Schmidt has found that the cells of tumor emboli in the pulmonary arterioles are able to penetrate the endothelium of the vessel only after they have been provided with a stroma from the subendothelial connective tissue. Our findings are easily explained on the basis thus suggested. A connective tissue highly cellular and perhaps still proliferating as the result of injury may well elaborate the stroma for a tumor more rapidly than normal connective tissue. Tests of growth in vitro support this idea. Connective tissue reacting to an injury grows profusely and almost immediately when incubated in plasma, whereas normal tissue from the same region shows usually no growth whatever. Dead tumor fragments in contact with the peritoneum cause a change favorable to the lodgment and growth of later tumor fragments. It seems not improbable that the peritoneal dissemination of certain human neoplasms may be accomplished indirectly through the death of the first tumor fragments cast off. Our observations have been purposely confined to the effects of injury on the peritoneal lining ; but they seem to afford the basis for a generalization. The secondary localization of tumors at points of injury may be attributed with good reason to the presence at such points of an active connective tissue capable of elaborating a stroma rapidly and abundantly. For it is the proliferation of the subendothelial connective tissue to form a supporting stroma that determines the fate of free tumor cells, whether these lie on the peritoneum or within a vessel.
Laboratories of The Rockefeller Institute for Medical Research.
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