Cancer invasion and metastasis remains the root cause of mortality. This process involves alterations of tumor microenvironment, particularly the remodeling of extracellular matrix, characterized by collagen IV uncoiling, degradation, fragments deposition and cross-linking. Quantum dots-labeled molecular probes are promising platforms to simultaneously study several subtle changes of key biomolecules, because of their unique optical and chemical properties. Here we report on a quantum dots-based imaging technology to study key components in tumor microenvironment during cancer progression, so as to gain new insights into the role of collagen IV plays, to define the cancer "invasion unit" and to develop the "pulse-mode" of cancer invasion.