Genetic Activities/Screening Approaches

The Invasion Signature -
Changes in Gene Expression in Migrating Breast Cancer Cell Lines

Data from John Condeelis Lab

Presented here are data from two invasive and metastatic subpopulations of tumor cells isolated from two different mammary tumor types (PyMT and MTLn3, Lin et al., 2002; Farina et al., 1998), which identify the pattern of gene expression characteristic of the "invasion signature". Data are presented as Expression Ratio for a range of genes identified in this signature. This ratio indicates the level of expression in an invasive compared to a general population of cells of a primary tumor, such that a high number indicated increased expression with invasive behavior.

These data indicate that invasive cancer cells are a population that is neither proliferating nor apoptotic but highly chemotactic to macrophage-secreted EGF. Of particular relevance to the migratory behavior of invasive cancer cells is the finding that the genes coding for pathways leading to the minimum motility machine, (the cofilin, capping protein and Arp2/3 pathways, that regulate -actin polymerization at the leading edge, and the directionality of cell protrusion during chemotaxis to EGF) are coordinately up-regulated. Key genes in the invasion signature have been studied for their ability to alter metastatic outcome and these results confirm the importance of the invasion signature in predicting metastasis (Wang et al., 2004). For further reading in this area go to the publication listing below (link this to the publication listing in the notes section).

MTLn3 invasive data

Additional tables: PyMT Invasive

Publications & Further Reading

Condeelis J, Singer RH, Segall JE. The great escape: When cancer cells hijack the genes for chemotaxis and motility. Annu Rev Cell Dev Biol. 2005; 21:695-718 PubMed.

Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion and metastasis. Cell 2006; 124:263-266. PubMed.

Farina KL, Wyckoff JB, Rivera J, Lee H, Segall JE, Condeelis JS, Jones JG. Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. Cancer Res. 1998; 58(12):2528-32. PubMed

Goswami S, Wang W, Wyckoff JB, Condeelis JS. Breast cancer cells isolated by chemotaxis from primary tumors show increased survival and resistance to chemotherapy. Cancer Res. 2004; 64:7664-7667. PubMed

Lin EY, Gouon-Evans V, Nguyen AV, Pollard JW. The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia. 2002; 7(2):147-62. PubMed

Wang W, Goswami S, Lapidus K, Wells AL, Wyckoff JB, Sahai E, Singer RH, Segall JE, Condeelis JS. Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res. 2004;64:8585-8594. PubMed

Wang W, Goswami S, Sahai E, Wyckoff JB, Segall JE, Condeelis JS. Tumor Cells caught in the act of invading: How they revealed their strategy for enhanced cell motility. Trends Cell Biol. 2005;15:138-145. PubMed

Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J. Direct visualization of macrophage mediated tumor cell intravasation in mammary tumors. Cancer Res. 2007; 67:2649-56. PubMed

Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 64:7022-7029 PubMed.

Wang W, Wyckoff JB, Goswami S, Wang Y, Sidani M, Segall JE, Condeelis JS. Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res. 2007; 67:3505-3511. PubMed