Spontaneous Tumors and their Isograft Models: Histopathology & Pathophysiology Studies

Our research focuses on the development of spontaneous tumors in mice and on how the age, genetic background, and immune status of the mice-as well as the presence or absence of specific genes-affect the histopathological characteristics of the tumors.

We study the incidence of spontaneous tumors and their pathological pattern in the natural setting of aged mice, which are kept alive for nearly their full normal life span. The animals are raised within a gnotobiotic colony that is free of life shortening intercurrent infectious diseases. We have found a high incidence of subcutaneous sarcoma in our aging C3Hf/Sed female mice. In our aging, retired FVB/N breeder mice, tumors are most commonly found in the lungs. The incidence of spontaneous T-cell thymice lymphomas in severe combined immunodeficient (SCID) mice is strikingly high. We have also published the first comprehensive report of spontaneous nonthymice tumors, including 8 myoepitheliomas and 3 rhabdmoyosarcomas, from our SCID retired breeders recently. Our results show that the incidence of spontaneous tumors and their morphological changes are markedly strain dependent, and are immune status, as well as age-associated.

We are documenting the development, growth, and histopathological characteristics of spontaneous tumors in the GFP transgenic mice with FVB background (such as VEGF-GFP/FVB, and Tie2-GFP/FVB mice). Our goal is to test the hypotheses that (a) the insertion of GFP reporter genes affects the incidence of spontaneous tumors in aging FVB genotobiotic mice, as well as changes their pathological patterns, and (b) spontaneous tumors developed in FVB-GFP transgenic mice exhibit different biological and molecular biological characteristics, such as different growth and metastatic potential, and different GFP expression in tumors as compared to the tumors in wild-type FVB mice.

We are also interested in developing novel tumor lines that are derived from the spontaneous tumors found in our laboratory. These tumor lines are used to study tumor pathophysiology in specific strains of transgenic mice derived from the same genetic background as the spontaneous tumors. One of our tumor lines, Os-P0107, is derived from a spontaneous osteosarcoma in a VEGF-GFP transgenic mouse; each of the cells in an Os-P0107 tumor expresses green fluorescent protein (GFP), which makes them easy to locate and track with intravital microscopy.

Another tumor line, LAP0297, is a lung adenocarcinoma with a high incidence of distant lung metastases. This line, which is ideal for the study of metastasis, is derived from a spontaneous lung tumor in a FVB/N mouse. For pre-clinical studies of antiangiogenesis therapy, we have used spontaneous autochthonous tumors and their isografts, implanted in aged C3Hf/Sed mice, to more accurately simulate the clinical conditions that affect many human cancer patients.