RESUMO
MIP-1alpha is a member of a family of proinflammatory cytokines produced by activated macrophages which has been shown to be a negative regulator of early hematopoietic stem cell progenitors. We report on results testing recombinant human (rh) MIP-1alpha on the clonal growth of different human nonhematopoietic tumor cell lines in vitro. Cell lines tested included the following histologies: 7 glioblastomas, 1 neuroblastoma, 2 head and neck carcinomas, 4 lung carcinomas, 3 colorectal carcinomas, 1 gastric carcinoma, 1 pancreatic carcinoma, 1 breast carcinoma, 1 prostate carcinoma, 1 choriocarcinoma, 1 ovary carcinoma, 1 osteosarcoma, and 3 melanomas. MIP-1alpha (0, 2, 20, 200 ng/ml) was tested in human tumor cloning assays (HTCA) in agar-containing capillaries (HTCAcap) and in mixtures of methylcellulose and agar (HTCAmix), representing assay systems with different plating efficiencies (PE). Tumor cells were continuously exposed to the cytokine for the complete assay period. Clonal growth of none of the cell lines was significantly and reproducibly stimulated or inhibited by MIP-1alpha.
RESUMO
In the present study we report that recombinant human (rh) interleukin 4 (IL-4) has direct, dose-dependent antiproliferative effects on the human lung cancer cell line CCL 185 in vitro as measured by a human tumor cloning assay (HTCA). The biological response of the tumor cells to rhIL-4 is correlated with expression of specific binding sites for human (h) IL-4 on the cell surface. Furthermore, we have xenotransplanted CCL 185 into BALB/c nu/nu mice. Subsequently, the mice were treated for 17 days with twice 0.5 mg/m2 rhIL-4 or control vehicle subcutaneously per day. Treatment with rhIL-4 yielded a significant inhibition of tumor growth versus control. Histology of the tumors in both groups showed no marked infiltration of the tumors with murine hematopoietic and lymphocytic cells consistent with the species specificity of IL-4. We conclude that rhIL-4 has direct antiproliferative effects on the growth of a human lung tumor cell line in vitro and in vivo which together with its regulatory effects on various effector cell populations makes this cytokine a possible candidate for experimental cancer treatment.
RESUMO
HL-60, a cell line originating from a human myeloid leukemia, expresses urokinase-type plasminogen activator (uPA) on the mRNA level and secretes the protein into the culture supernatant. Additionally, uPA receptors (uPA-R) could be detected in HL-60 on both the mRNA and the protein level, whereas the lymphoblastic cell line Raji studied in parallel was uPA-R negative. The cell lines were further studied in their clonal growth in methylcellulose under the influence of rhuPA (rhpro-uPA). The growth of Raji cells was not influenced by rhuPA. Colony and cluster formation of HL-60 was not reproducibly affected by rhuPA in concentrations between 1-100 ng/ml. In some experiments however, there were higher numbers of colonies in the HL-60 cultures incubated with rhuPA which was due to a cluster-to-colony shift. Furthermore, the HL-60 colonies in the rhuPA incubated plates always showed morphological alterations including an adherent basis indicating functional differentiation. This assumption was further supported by the observation that the secondary plating efficiency (PE2) of HL-60 cells taken from single colonies of uPA-incubated plates decreased significantly when compared with PE2 of cells from colonies grown without the presence of uPA. In conclusion, the intact uPA molecule functions like an autocrine cytokine for a human leukemic cell line, which in addition to its effects in tumor invasion makes it an interesting target molecule for further studies on tumor suppression.