Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling.

TLDR

The authors used GFP‑labeled breast cancer mouse models and multiphoton microscopy to image individual tumor cells in situ, then correlated observed behavioral differences with cDNA microarray data to pinpoint genes linked to invasion and metastasis. They identified five key behavioral distinctions between non‑metastatic and metastatic primary tumors—relating to extracellular matrix, motility, and chemotaxis—and linked these to seven classes of differentially expressed genes, demonstrating that in‑vivo cell behavior aligns with distinct gene expression patterns that illuminate tumor microenvironment mechanisms.

Abstract

We have developed animal models of breast cancer that allow the direct examination of the behavior of individual green fluorescent protein-expressing carcinoma cells in live nonmetastatic and metastatic primary tumors in situ. We have combined this model with multiphoton microscopy to image differences in cell behavior within the primary tumor. Differences in cell behavior between nonmetastatic and metastatic cells in culture and within live primary tumors were correlated with results from cDNA microarray analyses to identify potentially important genetic determinants for breast cancer invasion and metastasis. Using multiphoton microscopy, we found five major differences in carcinoma cell behavior between the nonmetastatic and metastatic primary breast tumors involving extracellular matrix, cell motility, and chemotaxis. Behavioral differences were correlated with seven categories of molecules that were differentially expressed and related to these behaviors. We have found that extracellular matrix composition, actin nucleation factors, molecules involved in mechanical stability and survival, and cell polarity and chemotaxis showed large and consistent differences in gene expression. We conclude that aligning cell behavior in vivo with patterns of gene expression can lead to new insights into the microenvironment of carcinoma cells in the primary tumor and the molecular mechanisms behind cell behavior.