28 Apr fibronectin-expressing mesenchymal tumor cells promote breast cancer metastasis
For cancer to metastasize, tumor cells must invade the local tissue and grow and proliferate once they arrive. Tumor cell heterogeneity, the presence of multiple types of cancer cells within a tumor, can increase cell proliferation and invasion through interactions, increasing the potential for metastasis. Also, pro-invasion cancer cells express the protein fibronectin and increase metastasis of pro-growth cancer cells. We investigated this interaction by analyzing these two cell types’ migration and survival, both alone and in cocultures. We discovered that pro-invasion cells have a protective effect on pro-growth cells, which otherwise die quickly in nutrient-starved conditions. Further, we found that adding soluble fibronectin to pro-growth cells in culture was sufficient to improve survival. However, their survival was higher for coculturing conditions. These studies highlight the importance of cancer cell heterogeneity and the role of fibronectin in metastasis.
Figure 1: (A) Image processing steps from raw image acquisition to segmentation of final cell boundaries, (B) cell parameterization and tracking, (C) proliferation of Ca1a (epithelial tumor cells), (D) velocity of Ca1a cells in monoculture and coculture within the microfluidic chamber, and (E) Ca1a cell trajectory maps in monoculture and coculture showing the total migration records of the representative 50 cells with the longest travel distance.
Figure 2: Epithelial to Mesenchymal Transition (EMT) markers in Ca1a cells upon fibronectin (FN) exposure within the well plate. The scale bar shows 100 µm. (A) Immunohistochemical staining for FN and DAPI on monocultured Ca1h cells, (B) Ca1h-FN30 cells, (C) Ca1a cells, (D) Immunoblotting with molecular weight markers and normalized intensity ratio, representing detection of EMT markers from Ca1a cells for FN content in their media, (E) Mean Euclidean and the sum of all distances traveled quantified for Ca1a, and (F) Ca1h cells across the culture conditions.