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Updated: Jul 8, 2026
Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Complete suppression of tumor formation by high levels of basement membrane collagen
Ann Harris1, Henry Harris, Michael A Hollingsworth
1Weatherall Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom. ann-harris@northwestern.edu
Abstract:
Suppression of tumorigenicity was first shown in hybrids produced by the fusion of a range of different highly malignant tumor cells with diploid fibroblasts. Cytogenetic analysis of these hybrids revealed that suppression involved a genetic region located in one specific chromosome donated to the hybrid cell by the fibroblast parent. The identity of the gene responsible for this dramatic effect has remained obscure. We now present strong evidence that the primary determinant is the gene specifying collagen XV, a proteoglycan closely associated with the basement membrane. We transfected a line of highly tumorigenic human cervical carcinoma cells with an expression vector carrying the full-length cDNA of the human collagen XV gene. We selected clones making various amounts of collagen XV, examined their growth in vitro, and tested their tumorigenicity in nude mice. High levels of collagen XV altered the growth properties of the cells in three-dimensional cultures. Moreover, we found that, in a dose-dependent manner, the production of collagen XV completely suppressed tumorigenicity in clones that synthesized this molecule at high levels. Immunohistologic studies suggest that suppression is associated with extracellular deposition of the proteoglycan at the cell periphery.
Insights
Tumorigenicity suppression in cancer cells is linked to collagen XV production. Introducing the collagen XV gene into cervical carcinoma cells significantly reduced their ability to form tumors.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Tumorigenicity suppression was initially observed in hybrids of malignant tumor cells and diploid fibroblasts.
- Cytogenetic analysis indicated a specific chromosome region from fibroblasts was responsible for suppression.
- The exact gene mediating this effect remained unidentified.
Purpose of the Study:
- To identify the gene responsible for suppressing tumorigenicity in cancer cell hybrids.
- To investigate the role of collagen XV (COL15A1) in tumor suppression.
Main Methods:
- Transfection of human cervical carcinoma cells with the full-length human collagen XV gene cDNA.
- Selection of clones producing varying levels of collagen XV.
- In vitro growth assays, including 3D cultures.
- In vivo tumorigenicity testing in nude mice.
Main Results:
- High levels of collagen XV production altered cancer cell growth properties in 3D cultures.
- Collagen XV production suppressed tumorigenicity in a dose-dependent manner.
- Immunohistology suggested extracellular deposition of collagen XV at the cell periphery correlated with suppression.
Conclusions:
- The gene encoding collagen XV is a primary determinant for suppressing tumorigenicity.
- Collagen XV plays a significant role in inhibiting cancer cell growth and tumor formation.
- Extracellular deposition of collagen XV may be a key mechanism in tumor suppression.
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