Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth

Abstract

We examined the extravasation and subsequent migration and growth of murine mammary tumor cell lines (D2A1 and D2.OR) which differ in their metastatic ability in lung and liver, invasiveness in vitro and expression of the cysteine proteinase cathepsin L. In light of the differences in invasiveness and cathepsin L expression, we hypothesized that during hematogenous metastasis the two cell lines would differ primarily in their ability to extravasate. We used in vivo videomicroscopy of mouse liver and chick embryo chorioallantoic membrane to examine the process and timing of extravasation and subsequent steps in metastasis for these cell lines. In contrast to our expectations, no differences were found between the cell lines in either the timing or mechanism of extravasation, at least 95% of cells having extravasated by 3 days after injection. However, after extravasation, the more metastatic and invasive D2A1 cells showed a greater ability to migrate to sites which favor tumor growth and to replicate to form micrometastases. These studies point to post-extravasation events (migration and growth) as being critical in metastasis formation.

Gelatinase-mediated migration and invasion of cancer cells

“…Similar results have also been obtained using tumor cell lines with low and high metastatic potential in mice and in the CAM assay. No difference in the extravasation rate was observed, whereas subsequent migration in the tissue and the rate of tumor cell proliferation were different (Koop et al, 1996;Morris et al, 1994). Thus whereas the spreading of the tumor cells into various organs from the primary tumor appears to be an efficient process, the subsequent growth of these metastasized cells is a rate-limiting step.…”

Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis

“…It has been reported that mammary carcinoma cells are localized beneath the capsule of Glisson 24 hr after metastasis induction. 62 Griffini et al 42 showed that 3 weeks after inoculation of CC531s cells, large metastatic nodules occur just beneath the capsule of Glisson, while few smaller and well-encapsulated nodules are only located in the center of the liver. Our experiments also demonstrated that cancer cells escaping the first line of immune defense during the first day of metastasis in both normal and NK-depleted rats were localized in the sinusoids, in the space of Disse or between parenchymal cells in a specific region that lies within 250 m beneath the capsule of Glisson.…”

EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

“…EZH2-and control virus-infected H16N2 cells were labeled with Fluoresbrite carboxylated polystyrene nanospheres of 48 nm diameter (Polysciences) as described (26). See Supporting Methods for details.…”