Table 1.
Integrin expression in indolent versus aggressive melanocytes.
| Study | Integrin (Direction of Regulation in Aggressive Melanocytes) |
Material Studied |
Method | Findings |
|---|---|---|---|---|
| Danen et al10 | ɑ2β1 (↑) ɑ6β1 (↑) | Human cells | FACS, IHC | Expression of laminin receptor ɑ6β1 and laminin/collagen receptor ɑ2β1 was low on non-metastatic or poorly metastatic cell lines but strongly expressed on highly metastatic cell lines. |
| Etoh et al11 | ɑ2β1 (↑) | Human cells | FACS | Enhanced migration on laminin and type IV collagen of several human melanoma cell lines is largely mediated by ɑ2β1 integrin. |
| Yoshinaga et al12 | ɑ2β1 (↑) ɑ3β1 (↑) | Human cells | FACS | A metastatic melanoma (MM) cell line expressed markedly increased levels of the β1, ɑ2, and ɑ3 subunits, but not the ɑ6 subunit, compared with a primary melanoma (PM) cell line. MM and PM cell migration was significantly inhibited by function-blocking anti-β1 and anti-ɑ3 MAbs but not by the anti-ɑ6 MAb tested. In contrast, the anti-ɑ2 MAb significantly inhibited MM but not PM cell migration. |
| Natali et al13 | ɑ3β1 (↑) | Human cells and tissue | IHC | Increased ɑ3β1 expression correlates with the degree of dermal invasion in primary lesions and is detectable in 82% of metastatic foci but only weakly expressed in benign nevi. |
| Vizkeleti et al14 | ɑ3β1 (↑) ɑ4β1 (↑) ɑvβ8 (↑) | Human cells and tissue | qRT-PCR | Analysis of select integrins (ɑ2, ɑ3, ɑ4, ɑ9, β5, β8, ɑ6, β1, and β3) highlighted the possible importance of ɑ3β1, ɑ4β1 and ɑvβ8 in the metastatic process and in distinguishing regional and distant metastases. |
| Danen et al15 | ɑ5β1 (↑) ɑvβ3 (↑) ɑ6β4 (↓) | Human tissue | IHC | ɑ5β1 and ɑvβ3 integrin are exclusively expressed in melanoma but not in nevi; expression of ɑ6β4 integrin is decreased in melanoma. |
| Ziober et al16 | ɑ6β1 (↑) ɑ7β1 (↓) | Murine cells | FACS, Northern & Western Blots | The study showed that highly metastatic murine melanoma cells lose ɑ7β1 integrin expression and upregulate ɑ6β1 integrin. |
| Kramer et al17 | ɑ7β1 (↑) | Human and murine cells | Western Blots | Laminin binding of ɑ7β1 integrin was detected in melanoma cells but not in normal melanocytes. |
| Hieken et al18 | β1 (↑) | Human tissue | IHC | β1 integrin expression in primary cutaneous melanoma was associated with occult regional lymph node metastasis. |
| Hieken et al19 | β1 (↑) ɑvβ3 (↑) | Human tissue | IHC | Integrin β1 and ɑvβ3 expression in intermediate thickness primary cutaneous melanoma was associated with an increased likelihood of disease recurrence and decreased long term survival. |
| Nikkola et al20 | β1 (↑) | Human tissue | IHC | Elevated integrin β1 expression was associated with shorter DFS and increased anti-apoptotic protein Bcl-2 expression in metastatic melanoma patients. |
| Albelda et al21 | ɑvβ3 (↑) | Human tissue | IHC, Western Blot | ɑvβ3 expression exclusively restricted to invasive vertical growth phase melanoma cells and melanoma metastases. |
| Felding-Habermann22 | ɑvβ3 (↑) | Human cells | Western Blot | Lack of ɑvβ3 expression strongly inhibits tumorigenicity of human melanoma cells in mice. |
| Montgomery23 | ɑvβ3 (↑) | Human cells | Functional Assays | ɑvβ3 melanoma cells have a growth and survival advantage in collagen. |
| Hsu24 | ɑvβ3 (↑) | Human cells and tissue | FACS, IHC, Western Blot | ɑvβ3 associates with the progression from radial growth to vertical invasive growth in primary cutaneous melanoma. |
| Van Belle et al25 | ɑvβ3 (↑) | Human tissue | IHC | ɑvβ3 is mostly absent in nevi but expressed in nearly all melanoma metastases. ɑvβ3 associates with the progression from radial growth to vertical invasive growth in primary cutaneous melanoma. |
| Voura et al26 | ɑvβ3 (↑) | Human cells | Functional Assays | Interaction of ɑvβ3 on melanoma cells with the L1 Cell Adhesion Molecule on endothelial cells plays and important role in the transendothelial migration of melanoma cells. |
| Meves et al27 | ɑvβ3 (↑) | Human tissue | IHC, qRT-PCR, RNAseq | ɑvβ3 expression in thin and intermediate thickness primary cutaneous melanoma was associated with an increased likelihood of sentinel lymph node metastasis within 90 days of diagnosis. |
Abbreviations: FACS, Fluorescence-activated cell sorting; IHC, immunohistochemistry; MAb, monoclonal antibody; qRT-PCR, qualitative reverse transcriptase polymerase chain reaction; DFS, disease free survival; RNAseq, next-generation RNA sequencing.