ABSTRACT

As much as 90% of cancer associated mortality follows metastasis of a primary tumor. Circulating tumor cells (CTCs) and CTC clusters are important for metastasis. Compared to CTCs, CTC clusters formed by collective invasion exhibit a 23−50 fold increase in metastatic potential, but the factors that influence collective invasion are largely unknown. Using well defined three-dimensional matrices and different extracellular matrix (ECM) concentrations, we found that cancer cells were more prone to collective invasion at low ECM concentration. Moreover, despite variation of biological factors, changes in ECM microarchitecture, especially the pore size of the matrix, was correlated with the probability of collective invasion, which indicates that the physical microarchitecture of ECM plays an important role in collective invasion of cancer cells.

摘要

高达90％的癌症相关死亡率是由于原发肿瘤的转移引起的。循环肿瘤细胞（CTC）和CTC簇对于转移非常重要。与四氯化碳相比，由集体入侵形成的四氯化碳簇的转移潜能增加了23-50倍，但是影响集体入侵的因素在很大程度上尚不清楚。使用定义明确的三维矩阵和不同的细胞外基质（ECM）浓度，我们发现癌细胞在低ECM浓度下更易于集体入侵。此外，尽管生物学因素有所变化，但ECM微结构的变化，特别是基质的孔径与集体入侵的可能性相关，这表明ECM的物理微结构在癌细胞的集体入侵中起着重要作用。