A rat model to study early micro‐metastases in the brain

Our long‐term goal is to exploit blood‐borne responding cells to attack microscopic tumor in the brain. Some form of micro‐tumor is characteristic of most tumors that grow in the brain, from infiltrative primary astrocytoma to blood‐borne micro‐metastases from other sites. This tumor is too small to image by standard methods, but blood‐borne cells are already adapted to survey the tissues, including the brain.∗ A good small animal model was needed. In our rat model, after intracarotid injection, tumor cells enter the brain and form metastases. Because the tumor and host are syngeneic, immunocompetent hosts can be used. Because tumor enters from the blood (rather than by direct injection), there is no wound to complicate interpretation of the response. The tumor cells express an enzyme marker, to aid detection in tissue sections. Histochemical stain for the marker reveals multiple parenchymal metastases at day 7.∗∗ Here, we describe detection of micro‐metastases at earlier times. METHODS. Fischer rats received intra‐carotid injection of syngeneic mammary carcinoma MATB/ap. These cells constitutively express placental alkaline phosphatase (ap) as a marker and surrogate tumor antigen. Rats were sacrificed after 2–3 days, and cryostat sections were stained histochemically, or with antibody, to reveal tumor. RESULTS. There appears to be a lag in marker expression; it is often not well‐expressed at day 2–3, and this is consistent with results in vitro. Early tumor is readily detected by antibody stain for keratin, as expected. Antibody to the glucose transporter, GLUT‐1, also stains the tumor cells. DISCUSSION. Being able to readily detect early micro‐metastases, the next step is to define the earliest populations of responding cells, and how their entry to tumor sites can be enhanced. Funded by NIH.