Cell Migration and Invasion

Danijela Vignjevic
Scientific keywords: actin cytoskeleton, cancer cell invasion, cell migration, tumor microenvironment
Technics Used in the Lab: Imaging of cells, tissues and whole animals including two-photon confocal, spinning-disk confocal, time-lapse, TIRF, electron microscopy, whole body imaging (IVIS), and colonoscopy. Standard cell biology, molecular biology and biochemistry techniques. Cell cultures in 2D and 3D matrices. Histology. Transgenic and xenograft tumor mouse models.

We are interested in how cancer cells interact with their microenvironment during invasion. In carcinoma in situ, the basement membrane represents a physical barrier that prevents spreading of the primary tumor to adjacent tissues. It is believed that cancer cells perforate basement membrane, but stromal cells such as carcinoma-associated fibroblasts (CAFs) also secrete matrix proteinases. Thus, the question is who is invading whom – do cancer cells invade the stroma or is the stroma invading tumor? Once the basement membrane is compromised, cancer cells migrate through the stroma towards the blood vessels, allowing dissemination of the tumor and formation of metastasis. Besides secreting growth factors that can stimulate invasive migration of cancer cells, CAFs can also actively excavate passageways in the extracellular matrix and lead cancer cell invasion. How cancer cells and CAFs cooperate during invasion of the stroma remains unclear. Finally, in collaboration with physicists we are asking if mechanical pressure imposed by stroma can have an additional role in stimulating cancer invasion.

Fig 1 Cancer cells and CAFs (red and blue) separated by native basement membrane (green).

Fig 1
Cancer cells and CAFs (red and blue) separated by native basement membrane (green).

Fig 2. Cancer cells (green) invading collagen (reflectance)

Fig 2. Cancer cells (green) invading collagen (reflectance)