Abstract: Objective To investigate the role of type I collagen as an autocrine protein in promoting the growth lung cancer cells
in a three-dimensional (3D) culture system. Methods Immunohistochemistry and RT-PCR were used to detect the expression
of type I collagen in lung cancer specimens and 5 lung cancer cell lines. The lung cancer cell lines in 3D cultures were treated
with vectors harboring short hairpin RNA (shRNA) targeting type I collagen, and the cell growth suppression was evaluated
using MTT assay and colony formation assay. The lung cancer cells stimulated with supernatant from lung cancer-derived
fibroblasts were tested for the expression of type I collagen mRNA. Results Type I collagen expressions were detected in both
the lung cancer tissues and the cell lines. In the 3D culture system, the growth of the cancer cell lines was obviously suppressed
by shRNA-mediated type I collagen knockdown evidenced by lowered cell growth rate and colony formation ability.
Stimulation with fibroblast culture supernatant resulted in enhanced expressions of type I collagen in the cancer cell lines.
Conclusion Autocrine of type I collagen I is required for maintaining lung cancer cell growth in 3D cultures, and its
expression is regulated by fibroblasts. These findings provide new insights into the role of type I collagen I in the tumor
microenvironment and point a new direction for targeted therapy of tumors.