A 3D biophysical model for cancer spheroid cell-enhanced invasion in collagen-oriented fiber microenvironment*

Abstract

The process of in situ tumors developing into malignant tumors and exhibiting invasive behavior is extremely complicated . From a biophysical point of view, it is a phase change process affected by many factors, including cell-to-cell, cell-to-chemical material, cell-to-environment interaction, etc. In this study, we constructed spheroids based on green fluorescence metastatic breast cancer cells MDA-MB-231 to simulate malignant tumors in vitro, while constructed a three-dimensional (3D) biochip to simulate a micro-environment for the growth and invasion of spheroids. In the experiment, the 3D spheroid was implanted into the chip, and the oriented collagen fibers controlled by collagen concentration and injection rate could guide the MDA-MB-231 cells in the spheroid to undergo directional invasion. The experiment showed that the oriented fibers greatly accelerated the invasion speed of MDA-MB-231 cells compared with the traditional uniform tumor micro-environment, namely obvious invasive branches appeared on the spheroids within 24 hours. In order to analyze this interesting phenomenon, we have developed a quantitative analyzing approach to explore strong angle correlation between the orientation of collagen fibers and invasive direction of cancer cell. The results showed that the oriented collagen fibers produced by the chip can greatly stimulate the invasion potential of cancer cells. This biochip is not only conducive to modeling cancer cell metastasis and studying cell invasion mechanisms, but also has the potential to build a quantitative evaluation platform that can be used in future chemical drug treatments.

Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

“…3(a2)b. Following the analysis method reported in the literature, the alignment direction of collagen fibers was analyzed using curvelet-based alignment analysis software (University of Wisconsin at Madison, USA), [30,31] and the results are shown in Figs. 3(b1) and 3(b2).…”

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments

“…Thus, the differences in the collagen fiber structure may result in different physiological behaviors between early and late-stage breast cancer cells. [8][9][10][11][12] It is worth noting that most current breast cancer drug screening protocols do not have the function of controlling the generation of collagen fiber structures and complex biochemical gradients to simulate the extracellular matrix of the microenvironment in vivo. [13][14][15] Specifically, these in vitro tumor models did not simultaneously reproduce the interactions between cell-fiber and cell-drug gradients better to evaluate the efficacy of drugs for breast cancer treatment.…”