Conversion of a Poorly Differentiated Human Adenocarcinoma to Ascites Form With Invasion and Metastasis in Nude Mice: Brief Communication

Abstract

Cells (1 X 10(7)/0.5 ml) from a Borrmann type III poorly differentiated adenocarcinoma of the human stomach were injected ip into nude mice. The injection resulted in ascites carcinoma with invasion (carcinomatous peritonitis) and liver metastasis. The inoculum was obtained from subcutaneous tumors at passage 9 in nude mice that had received serial transplants from the patient with Borrmann type III poorly differentiated adenocarcinoma of the stomach. Serial transfers of 1.5 X 10(6) dispersed cancer cells/0.5 ml into the peritoneal cavity of nude mice converted this adenocarcinoma to an ascites form. Hemorrhagic ascites accumulated within 3 weeks at the first passage and 4-6 weeks in serial passages. Carcinomas peritonitis occurred consistently and was observed in the diaphragm, mesenteries, omentum, and pancreas; metastases were seen in the liver and spleen. Subsequently, iv injection of ascites at passage 3 (6 X 10(5) cells/0.2 ml) into nude mice produced metastatic lesions in the lung and the heart. The histology of the invasive and metastatic lesions in the nude mice was similar to that of the original tumor in the patient with stomach carcinoma.

Metastasis of human tumors in athymic nude mice

“…(1976), who observed metastasis of a malignant hamster tumor transplant only when the tumors had grown to a large size and had penetrated th-body wall. Similarly, Takahashi et al (1978) and Kyriazis et a/. (1978), observed that metastasis can be induced by the simple expedient of using the intraperitoneal, rather than subcutaneous, route of tumor transplant.…”

Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis

“…Some tumor cells implanted subcutaneously into the cranial aspect of the nude mouse grow faster and produce more metastases than tumor cells implanted subcutaneously into the posterior body aspect [50]. The intraperitoneal injection of human solid tumor cells can produce ascitic growth with local infiltration followed by production of distant metastases [43,51,52]; these very same tumor cells, however, were not invasive when implanted subcutaneously. Similarly, lack of invasion in an HCC tumor line was associated with a host response manifested by formation of a dense capsule composed of connective tissue.…”

Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis

“…Multifocal metastases and widespread carcinomatosis resulting from the i.p. route of tumor cell injection have been attributed to improved tumor vascularity and the absence of the restrictive fibrous sheath (71,73). Recently, Witte and Ber (77) reported the improved growth of hybridoma cells injected into the spleens of recipient mice, and consideration of these findings led Kozlowski et al (65) to inject human tumor cells into nude mice by different routes, including the spleen.…”