Collagen matrix reorganization by tumor cells facilitates local invasion of tumor cells. Combined MPE/SHG imaging of tumor explants cultured within 3D collagen gels for eight hours demonstrates that tumor cells reorganize a previously random matrix to facilitate invasion. (A) Region of 3D collagen gel remote from the tumor demonstrating the random orientation of collagen present within 3D collagen gels in a region that has not been reorganized by a specific outside force. This random organization is specifically altered by cells from tumor explants as the cells contract and reorganize the collagen matrix. Similar to data in live intact tissues, non-invading regions show collagen pulled in near the explant but wrapped around the tumor boundary (B), while at regions of tumor cell invasion into the collagen gel, collagen has been radially aligned by the tumor cells (white arrow heads C) with cells (*) in direct contact with the collagen matrix (white arrowheads; D). Therefore, at regions of tumor cell invasion, collagen has been reorganized to a radial alignment from a random orientation, indicating a structural realignment of collagen fibers facilitates local invasion. Scale bar equals 25 μm.
Provenzano et al. BMC Medicine 2006 4:38 doi:10.1186/1741-7015-4-38