| Objectives1. It's well known that cell is the basic unit for all life activity, and interaction and signal transduction between cell and cell and between cell and extracellular matrix are the essence of basic phenomenon such as tumor invasion and metastasis. So the model of mouse blastocysts co-cultured with malignant tumor cells was established to explore dynamic interaction and difference in the invasive potential and its related gene expression between the two kinds of life cells under the same microenvironment in vitro. Thus, we intended to elucidate the intrinsic mechanisms of the two kinds of life phen- omenon from cytosociology and microenvrionment angle.2. As we knew, synergetic maladjustment between oncogenes and tumor suppressor genes is the important mechanisms for tumor invasion and metastasis. So the action of tumor suppressor genes, as negatively regulatory molecule, in the signal transduction pathway of trophoblastic cells orderly invading maternal endometrium in vivo was explored to elucidate the molecular mechanisms and therapeutic targets for malignant tumor cells form embryo implantation angle as an anti-tissue invasion model.3. Effects of mifepristone, as a drug of anti-blastocyst invasion, on the growth, invasion and metastasis of human gastric cancer SGC-7901 cells in vitro and in vivo were explored to promote the crossing of methodology and philosophic thinking between both disciplines and to offer new idea for clinical therapy of malignant tumor.SignificanceHigh speed and order proliferation and differentiation of early embryo(called by benign tumor), and trophoblastic cell orderly invading maternal endometrium establish anatural experiment(molecule) model for the study on the intrinic mechanisms of uncon- trollable proliferation, invasion and metastasis of malignant tumor cells. So the crossing and confluence of methodology and philosophical thinking between both will offer new idea for elucidating the intrinic mechanisms and clinical therapy for the two biological puzzles. Materials and methods1. The models of mouse blastocysts co-cultured with normal cell strains(the L929 and NIH3T3 mouse fibroblasts, the 9HTE human tracheal epithelial cells and the ECV- 304 human umbilical vein endothelial cells), with malignant tumor cell strains form differently histological origins(the HNE1 human nasopharyngeal carcinoma cells, the BGC-823 and SGC-7901 human gastric cancer cells, the 786-0 human kidney carcinoma cells, the BIU-87 and BADM-60 human bladder carcinoma cells, the Ros17/2.8 and Saos-2 human osteoblastoma cells, the RL95-2 human endometrial carcinoma cells and the SHZ-88 rat breast carcinoma cells), with human hepatocarcinoma cell strains (HepG2, SMMC-7721, QGY-7703 and MHCC97-H) and human breast carcinoma cell strains (T47D, MCF-7, ZR75-30, Bcap-37, MDA-MB-231 and MDA-MB-435s) were establish- ed to explore the interaction and whole biological behaviors changes of the two kinds of life cells under the same microenvironment in vitro.2. Morphological changes of malignant tumor cells and mouse blastocysts in the co-cultured system were assesed with H.E staining, Giemsa staining, methyl green- pyronin stainig and scanning electron microscope. Immunocytochemical staining and in situ hybridizaition were used to determined expression of integrin αv, focal adhesion kinase(FAK), matrix metalloproteinase-9(MMP-9), CD44v6, Cyclin D1 protein and Ki-67 mRNA in the co-cultured system.3. Immunohistochemical staining and in situ hybridization were used to exlpore the action of p16INK4a protein and nm23/NDPK mRNA, as tumor suppressor genes, in the signal transduction pathway of trophoblastic cell orderly invading endometrium in vivo. 4. Effects of mifepristone, as a drug for anti-blastocyst implantation, on the growth, invasion and metastasis of human gastric cancer SGC-7901 cells were explored by cellculture in vitro and the xenografted tumor model by the transplantation of the SGC-7901 human gastric cancer cells underneath the skin of BALB/c nude mice...
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