Temperature-dependent metastasis of the Lucke renal carcinoma and its significance for studies on mechanisms of metastasis

Abstract

Metastasis is temperature dependent in the renal adenocarcinoma of the North American leopard frog, Rana pipiens. Widespread, multiple, metastatic colonies occur in tumor-bearing frogs kept at 28 degrees C for 50 days while tumor-bearing frogs kept at 7 degrees C for 98 days or more have either no secondary deposits or they have only an occasional small metastatic nodule. An attractive aspect of the frog tumor is that invasion and metastasis can be permitted or inhibited by the manipulation of temperature alone-no exogenous chemicals or drugs are required for the effect. Because of this, biological variables which reproducibly and specifically associate with metastasis permissive conditions when ambient temperature is cycled between permissive and inhibitory values are strong candidates for being causal elements in the multistep process leading to metastasis. Intravascularly injected labelled renal tumor cells reached all organs studied in as little as 15 minutes at both metastasis restrictive and permissive temperature. The results with tumor cell inoculation dispose of the possibility that failure of metastasis in chilled animals is due to cold-induced changes in blood flow. Histologically typical metastatic colonies developed in frogs, kept at the permissive temperature, after injection with disaggregated tumor cells which were previously cryopreserved. Frog tumors elaborate type I collagenase in a temperature dependent manner. Type IV collagenase has been demonstrated as well. Tumor cell detachment in vitro, assembly and disassembly of tumor cell cytoplasmic microtubules, and invasion in vitro, are all temperature dependent.

Cyprinid Herpesvirus 3

“…For example, anguillid herpesvirus 1 (AngHV-1), infecting Japanese eel (Anguilla japonica) and European eel (Anguilla anguilla), only propagates in eel kidney 1 cells between 15 and 30°C, with an optimum around 11 Cyprinid Herpesvirus 3 20-25°C (Sano, Fukuda, & Sano, 1990; . In vivo, replication of ranid herpesvirus 1 (RaHV-1) is promoted by low temperature, whereas induction of tumor metastasis is promoted by high temperature (McKinnell & Tarin, 1984). In general, fish herpesvirus-induced infection is less severe or even asymptomatic if the ambient water temperature is suboptimal for virus replication, which explains the seasonal occurrence of certain fish herpesviruses, including CyHV-3 (Gilad et al, 2003).…”

Inappropriate gene expression in human cancer and its far-reaching biological and clinical significance

“…In this poikilothermic animal, renal adenocarcinomas induced by herpes viruses [72] display temperature-dependent metastatic behavior [73,74]. Tumor-bearing animals maintained at 7°C do not develop metastases, whereas those kept at 17°C or at 28°C have progressively more secondary growths [73].…”

Herpesviruses of Fish, Amphibians and Invertebrates

“…Tumour formation could be induced by injection with purified RaHV-1 (Mizell et al, 1969), and Koch-Henle's postulates were fulfilled (Naegele et al, 1974). Virus replication is promoted by low temperature (Granoff, 1999), whereas induction of metastasis is promoted by high temperature (Lucké & Schlumberger, 1949;McKinnell & Tarin, 1984). Although RaHV-1 cannot be cultured in cell lines, it was the first amphibian herpesvirus subjected to extensive genomic studies .…”