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Updated: Aug 18, 2026
Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Destruction of extracellular matrices containing glycoproteins, elastin, and collagen by metastatic human tumor cells
Abstract:
Four human tumor cell lines were grown in direct contact with the extracellular matrix proteins which had previously been produced by cultured rat smooth muscle cells. The extracellular matrix contained glycoproteins, elastin, and collagen, and its digestion by the tumor cells was followed by the appearance of radioactive breakdown products in the supernatant medium. All four tumor lines tested digested glycoproteins present in the matrix, whereas human fibroblasts were inactive in glycoprotein digestion. The human fibrosarcoma cell line (HT1080) demonstrated elastolytic and collagenolytic activity in addition to a plasmin-induced hydrolysis of glycoproteins. Removal of glycoproteins from the matrix was necessary for the maximal digestion rate of elastin and collagen, and plasmin generation by the tumor cell plasminogen activator therefore played a pivotal role in the hydrolysis of all of the matrix components. The elastolytic and collagenolytic activities were localized to the plasma membrane since no matrix digestion occurred unless the tumor cells were grown in direct contact with the connective tissue proteins. These activities were not inhibited by a wide spectrum of protease inhibitors. The degradation of elastin and collagen required active protein synthesis suggesting a relatively short half-life for the degradative enzyme(s). These quantitative studies, in which tumor cells were grown in contact with a complex extracellular matrix possessing some of the characteristics of connective tissue, should have a bearing on tumor cell invasion.
Insights
Human tumor cells actively degrade extracellular matrix proteins like glycoproteins, elastin, and collagen. This matrix digestion, crucial for tumor invasion, involves cell-surface enzymes and active protein synthesis.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- The extracellular matrix (ECM) provides structural support and influences cell behavior.
- Tumor cell invasion requires degradation of the surrounding ECM.
- Understanding ECM-ECM interactions is key to cancer research.
Purpose of the Study:
- To investigate the matrix-degrading capabilities of human tumor cell lines.
- To elucidate the mechanisms and components involved in ECM hydrolysis by tumor cells.
- To assess the role of ECM degradation in tumor cell invasion.
Main Methods:
- Culturing human tumor cell lines and human fibroblasts in direct contact with rat smooth muscle cell-derived ECM.
- Quantifying the digestion of ECM components (glycoproteins, elastin, collagen) using radioactive breakdown products.
- Investigating the role of plasminogen activator and plasmin in ECM hydrolysis.
- Localizing degradative activities to the cell surface and assessing the requirement for protein synthesis.
Main Results:
- All four tested human tumor cell lines digested ECM glycoproteins, unlike human fibroblasts.
- The HT1080 fibrosarcoma cell line exhibited elastolytic and collagenolytic activity.
- Glycoprotein removal was essential for maximal elastin and collagen digestion rates.
- Plasmin generation by tumor cell plasminogen activator was critical for hydrolyzing all ECM components.
- Degradative activities were cell-surface localized and required active protein synthesis, indicating enzymes with short half-lives.
Conclusions:
- Human tumor cells possess significant extracellular matrix-degrading capabilities, particularly glycoproteins, elastin, and collagen.
- Tumor cell-mediated ECM degradation, involving cell-surface enzymes and plasmin generation, is a crucial step in tumor invasion.
- These findings provide insights into the mechanisms underlying tumor cell metastasis and suggest potential therapeutic targets.
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