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Updated: Sep 20, 2026
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
Specific alpha v integrin receptors modulate K1735 murine melanoma cell behavior
Yongjian Yang1, Dongmin Dang, Amha Atakilit
1Department of Stomatology, University of California at San Francisco, San Francisco, CA, USA.
Abstract:
Expression of beta 3 integrins is increased in invasive melanoma. In this study we show that K1735 cell proliferation is enhanced by the expression of either beta 3 or a constitutively active Src. We investigated possible modulators of FN matrix assembly and found that matrix metalloproteinase 2 (MMP2) was activated by alpha v beta 3. alpha v beta 3 integrin was localized to focal contacts whereas alpha v beta 5 was peripherally distributed. MMP2 was also activated by expression of CASrc. MMP2 activation inversely correlated with FN matrix assembly, in that it dramatically reduced the organization of a FN matrix. K1735 cell migration on VN and invasion through a reconstituted basement membrane were decreased in the presence of anti-MMP2 antibodies. These results demonstrate that the expression of the alpha v beta 3 complex modulates melanoma cell behavior including activation of Src, organization of the cytoskeleton, assembly of the extracellular matrix, cell motility, and activation of MMP2.
Insights
Melanoma cell proliferation and invasion are influenced by beta 3 integrins. This study shows alpha v beta 3 integrin activates matrix metalloproteinase 2 (MMP2), impacting melanoma cell behavior and extracellular matrix organization.
Area of Science:
- Cell Biology
- Oncology
- Biochemistry
Background:
- Increased expression of beta 3 integrins is observed in invasive melanoma.
- Integrins play crucial roles in cell adhesion, migration, and signaling.
Purpose of the Study:
- To investigate the role of alpha v beta 3 integrin in modulating melanoma cell behavior.
- To identify modulators of fibronectin (FN) matrix assembly and their impact on melanoma progression.
Main Methods:
- K1735 melanoma cells were used to study the effects of beta 3 integrin and constitutively active Src expression.
- Activation of matrix metalloproteinase 2 (MMP2) was assessed in relation to alpha v beta 3 integrin and CASrc expression.
- Cell migration and invasion assays were performed in the presence of anti-MMP2 antibodies.
Main Results:
- Alpha v beta 3 integrin expression enhanced K1735 cell proliferation.
- Alpha v beta 3 integrin activated MMP2, which inversely correlated with fibronectin (FN) matrix assembly.
- MMP2 activation by alpha v beta 3 and CASrc led to reduced FN matrix organization.
- Inhibition of MMP2 decreased K1735 cell migration and invasion.
Conclusions:
- The alpha v beta 3 integrin complex significantly modulates melanoma cell behavior.
- This modulation includes effects on Src activation, cytoskeleton organization, extracellular matrix assembly, cell motility, and MMP2 activation.
- Targeting MMP2 may represent a therapeutic strategy for invasive melanoma.
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