Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology

Abstract

Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-a secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases.Key words: allergy -autoimmune disease -melanomaosteopontin -psoriasis -skin disease Please cite this paper as: Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology. Experimental Dermatology 2009; 18: 750-759.

The role of osteopontin expression in melanoma progression

“…By performing immunohistochemistry on the primary melanoma specimens, we observed increased OPN protein levels in samples with poor prognosis. Notably, increasing immunostaining was significantly associated with Breslow tumor thickness and metastatic capacity, indicating a role for OPN in melanoma progression [7,24]. However, our protein and gene expression results did not reveal clear relationships in all samples, and on average, we observed that increased OPN mRNA levels were associated with strong antigen positivity.…”

“…In human malignant melanoma, OPN expression is significantly associated with reduced relapse-free survival and additional histological parameters that are associated with poor clinical outcome [7,24,29,33]. OPN is a prognostic marker in a variety of cancers [30,[39][40][41].…”

“…Osteopontin (OPN) is a multifunctional extracellular matrix protein that is produced by numerous cell types [6][7][8][9][10][11]. OPN plays important roles in cancer cell adhesion, cell motility, and survival [12][13][14][15][16].…”

Metabolic Syndrome and Elevatedosteopontin: Their Associated Comorbidities in Patients With Psoriasis.

“…OPN is produced by different cell lines and binds to several integrin receptors and is known to induce cell adhesion, migration, and survival of immune cells including neutrophils, macrophages, T cells, mast cells, and osteoclasts [14].Secreted OPN appears to have a role in the development of psoriasis through inhibiting keratinocyte apoptosis, thereby supporting enhanced epidermal proliferation. OPN promotes vessel formation subsequently supporting the influx of inflammatory cells.OPN has a pro-angiogenic effect on microvascular endothelial cells, and has been involved in the onset of angiogenesis through a mechanism mediated by IL-1 [15].Moreover, there are reports suggest that OPN and MMP-9 may be regulated by TNFα, indicating that they may have a role in the pathogenesis of psoriasis We aimed to assess metabolic syndrome and osteopontin and their associated systemic comorbidities in patients with psoriasis In our study, FBS level was found to benonsignificantlymore in psoriatic cases rather than control. Cholesterol, LDL-c, TG levels weresignificantly elevated, andHDL-c levels were lowerin psoriatic cases than control.…”

“…OPN secreted by keratinocytes, possibly stimulated through IFN γ from T-cells and OPN from effector T cells attract additional inflammatory cells [15].…”