CCN2 and neoplasm: When we further quantified the intra-tumoral collagen I fibers by second harmonic generation (SHG) imaging using two-photon laser scanning microscope, the results showed that not only the fibrous areas were enlarged in the over-CTGF-HMLER tumors, the average intensity of each fiber was increased which may due to the fibrotic self-assembly, and further, we detected ~30% of the fibers aligned perpendicular to the over-CTGF-HMLER tumor edges, which provided a path for the tumor cells to follow and encouraged spreading [29].