Fabra A, Nakajima M, Bucana C D, Fidler I J
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Differentiation. 1992 Dec;52(1):101-10. doi: 10.1111/j.1432-0436.1992.tb00504.x.
We examined whether fibroblasts from subcutaneous, colon or lung tissues of nude mice influence the invasive potential of highly metastatic human colon carcinoma KM12SM cells. Primary cultures of nude mouse fibroblasts from skin, lung and colon were established. Invasive and metastatic KM12SM cells were cultured alone or with fibroblasts. Growth and invasive properties of the KM12SM cells were evaluated as well as their production of gelatinase activity. KM12SM cells were able to grow on monolayers of all three fibroblast cultures but did not invade through skin fibroblasts. The conditioned media of KM12SM cells cocultured with skin, colon or lung fibroblasts were examined for the presence of type IV collagenase (gelatinase). KM12SM growing on plastic and on colon or lung fibroblasts produced significant levels of latent and active forms of 64 kDa type IV collagenase, whereas KM12SM cells cocultivated with nude mouse skin fibroblasts did not. In contrast, human squamous cell carcinoma A431 cells produced significant levels of collagenase type IV when cocultured with nude mouse skin fibroblasts, a tissue they invaded and completely penetrated. Incubation of KM12SM cells in serum-free medium containing recombinant human interferon-beta (fibroblast interferon) was associated with significant reduction in gelatinase activity. Since the production of type IV collagenase by human colon cancer cells is specifically inhibited by mouse skin fibroblasts but not by colon or lung fibroblasts the data suggest that organ-specific fibroblasts can influence the invasive and metastatic properties of KM12SM cells.
我们研究了裸鼠皮下、结肠或肺组织中的成纤维细胞是否会影响高转移性人结肠癌KM12SM细胞的侵袭潜能。建立了来自皮肤、肺和结肠的裸鼠成纤维细胞原代培养物。侵袭性和转移性的KM12SM细胞单独培养或与成纤维细胞共同培养。评估了KM12SM细胞的生长和侵袭特性以及它们的明胶酶活性产生情况。KM12SM细胞能够在所有三种成纤维细胞培养物的单层上生长，但不会穿过皮肤成纤维细胞进行侵袭。检测了与皮肤、结肠或肺成纤维细胞共同培养的KM12SM细胞的条件培养基中是否存在IV型胶原酶（明胶酶）。在塑料上以及在结肠或肺成纤维细胞上生长的KM12SM细胞产生了显著水平的64 kDa IV型胶原酶潜伏形式和活性形式，而与裸鼠皮肤成纤维细胞共同培养的KM12SM细胞则没有。相比之下，人鳞状细胞癌A431细胞与裸鼠皮肤成纤维细胞共同培养时产生了显著水平的IV型胶原酶，裸鼠皮肤是它们能够侵袭并完全穿透的组织。将KM12SM细胞在含有重组人干扰素-β（成纤维细胞干扰素）的无血清培养基中孵育，与明胶酶活性显著降低有关。由于人结肠癌细胞产生IV型胶原酶受到小鼠皮肤成纤维细胞的特异性抑制，而不受结肠或肺成纤维细胞的抑制，这些数据表明器官特异性成纤维细胞可以影响KM12SM细胞的侵袭和转移特性。
