Fibroblast Promotes Head and Neck Squamous Cell Carcinoma Cell Invasion through Mechanical Barriers in 3D Collagen Microenvironments

Yin Quan Chen*, Jean Cheng Kuo, Ming Tzo Wei, Ming Chung Wu, Muh Hwa Yang, Arthur Chiou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Cancer metastasis involves not only cancer cells but also fibroblasts and the surrounding collagen matrices. Previous studies have reported that in tumor tissues, cancer cells and fibroblasts surrounded by dense collagen are often associated with a high risk of cancer metastasis. However, the mechanism of the interaction between the cancer cells, fibroblasts, and the surrounding collagen matrices in vivo to promote cancer cell invasion in different collagen concentration environments remains unclear. To address this issue, we cocultured head and neck squamous cell carcinoma (OECM-1 cells) and human dermal fibroblasts (HDFs) to form 3D spheroids, embedded in collagen gel with different concentrations to delineate their roles and their interactions in cancer cell invasion. We showed that in single-species spheroids, the OECM-1 cells could not remodel the high-concentration (8 mg/mL) collagen matrices to invade into the surrounding collagen. In contrast, in the coculture spheroids, the HDF cells could remodel the collagen matrices, via MMP-meditated collagen degradation, to increase the invasion capability of OECM-1 cells. In the case of low-concentration (2 mg/mL) collagen matrices, both HDF and OECM-1 cells in the coculture spheroids could independently invade into the surrounding collagen via force remodeling of collagen. Our results revealed that the assistance of HDFs was critical for OECM-1 cell invasion into the surrounding extracellular matrix with high collagen concentration, high storage modulus, and small pore sizes. These insightful results shed light on the possible optimal invasion strategy of cancer tumors in vivo in response to different storage moduli of surrounding collagen matrices.

Original languageEnglish
Pages (from-to)6419-6429
Number of pages11
JournalACS Applied Bio Materials
Issue number9
StatePublished - 21 Sep 2020


  • 3D coculture spheroids of fibroblasts and cancer cells
  • 3D collagen matrices
  • cancer invasion capability
  • collagen concentration
  • force remodeling of collagen
  • MMP-meditated collagen degradation


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