ABSTRACT
The tumor stroma comprising the extracellular matrix, mesenchymal cells, inflammatory cells, and a supporting network of blood vessels, lymphatic vessels, and nerves was traditionally believed to play a passive role in the regulation and development of cancer. Imaging of protease activity in tumor models has been primarily performed using near-infrared optical imaging of protease-activated probes. Despite major advances in intravital microscopy and optical imaging techniques, dynamic, noninvasive, in vivo investigations of the tumor-host tissue interface remain a challenge. Visualization of the initial invasion of tumor cells through the lymphatic system into the subcapsular sinuses and eventually into the parenchyma of the lymph nodes was recently demonstrated with in vivo fluorescence microscopy in an orthotopic human breast cancer model. These studies were performed in conjunction with measurements of interstitial fluid pressure (IFP) and suggest that intravasation of cancer cells into the lymphatic system may be mediated through IFP.
