Solid cancer tumors grow into various shapes. These shapes primarily arise from the unregulated proliferation of cells and are often cited as metrics to gauge the prognosis of the disease. However, growth is only the beginning of the lethal journey of a tumor. While more than 90% of cancer-related death is caused by metastasis, it is unclear how tumor geometry modulates the dissemination of cancer cells. To investigate this problem, we combine experimental measurements and computational modeling to study the dissemination of tumors in the 3-D extracellular matrix (ECM). We find that the tumor geometry and its rate of dissemination are indeed closely related via a mechanical feedback mechanism. Tumor shape determines the collective ECM remodeling by cell-generated forces while the micromechanics of the remodeled ECM regulate the migration and force generation of tumor cells.

The cover image of the March 10 issue of Biophysical Journal is a two-channel confocal slice of a star-shaped tumor at the onset of invasion into the surrounding ECM. Here the ECM consists of FITC-conjugated type I collagen matrix, and the tumor is a cluster of fluorescently labeled MDA-MB-231 cells. The initially random alignment of the collagen fibers is reconfigured by cell spreading and contraction after the cells are seeded. The cell cluster is fully enclosed in a 3-D collagen matrix. Cells at the boundary have extended long protrusions into the collagen matrix.

Both the cover image and our research highlight the importance of physical interactions in cancer metastasis. Our tissue is mechanically reconfigurable, which means it can be exploited by tumors to facilitate their growth and invasion. It also offers us opportunities to curb the progression of this deadly disease. We hope this largely unexplored research field can attract more interdisciplinary research, eventually leading to complimentary therapeutic options to cancer patients.

—Jihan Kim, Yu Zheng, Amani Alobaidi, Hanqing Nan, Jianxiang Tian, Yang Jiao, Bo Sun