Effect Of Matrix Rigidity On Organ-specific Tumor Cell Arrest And Adhesion By Flow

Tumor metastasis, a main biological characteristic of malignance tumor, is animportant cause of death for most cancer patients. During the tumor metastasis, thearrest and adhesion of tumor cells within microvessels is not only an initial step oftumor metastasis in blood vessel, but also a vital process for the organ-specificmetastasis. Recent research results showed that, the tumor cells in blood circulation arecaptured in capillary. But, the action of tumor cell adhesion is not random, it existsprominent organ discrepancy (named as organ specificity of tumor metastasis). Themost common target organs are lung for breast cancer metastases, followed by liver,bone, and it is rarely found in other organs. However, the organ-specific mechanism oftumor cells firstly adhered to microvessels, which is important for studying theorgan-specific metastasis, still remains elusive. By using the parallel plate flow chamberto simulate the blood flow in vivo environment, this paper explores the effect of matrixmechanics on tumor cell arrest and adhesion in specific target organ, as well as analyzethe correlation between the expression of integrin β1and adhesion behavior. The resultswill contributes to understand and cognize the effect and mechanism of matrixmechanical properties of distinct organ on tumor cell arrest and adhesion in blood vessel,and provide a theoretical foundation for treating cancer disease, as well as developingnew drugs for tumor metastasis. Here, the concrete works and conclusions are as thefollowing:Object: By analyzing and comparing the effect of hemodynamics and matrix rigidity onthe tumor cell arrest and adhesion behaviors with/without endothelial cells andchemokines, this paper will discuses1) Whether matrix rigidity is involved in theregulation of organ-specific tumor cell arrest and adhesion or not, and what is theregular pattern?2) In definite matrix mechanics, whether endothelial cells andchemokines are involved in the regulation of tumor cell arrest and adhesion or not, andwhat is the regular pattern?3) What is the role of integrin β1in this process? Thisstudy will contribute the understanding of tumor cell capture and adhesion behaviors inblood microvessels.Method: Here, we use the polyacrylamide gel membrane to simulate the matrixmechanical properties of different organs or tissues, and flow chamber test in vitro toquantitative analysis of cell arrest and adhesion under different experimental conditions, and also detect the expression and function of integrin β1on tumor cells surface byFlow Cytometry and flow chamber.Results:1) Matrix mechanics regulate the capture and adhesion behavior of tumor cellsby flow, which facilitate tumor cells to favorably adhere on the substrate that the matrixrigidity similar to breast cancer tissue(about5kPa);2) Endothelial cells cultured on thesubstrate of different matrix rigidity，significantly promote the capture and adhesion oftumor cells. The largest number of adhered tumor cells is the5kPa group, then is the10kPa group, the least is about2kPa group;3) Integrin β1is involved in the regulationof tumor cell arrest and adhesion, and it significantly reduce the number of adheredtumor cells when blocked out the integrin β1receptor sites of tumor cells by integrin β1antibody;4) SDF-1can regulate the expression and function of integrin β1on thesurface of tumor cells, and enhance the adhesion number of breast tumor cells toendothelial cells in specific matrix mechanics conditions.The results of this study can preliminarily showed that the organ-specific captureand adhesion behaviors of tumor cells depends on matrix mechanics by flow in vitro,and may contributes to draw a conclusion that the phenomenon that organ-specificmechanical properties regulated the organ specify of tumor cell capture and adhesionbehavior may indeed exist in vivo.