4.1 Article

The role of osteopontin expression in melanoma progression

Journal

TUMOR BIOLOGY
Volume 36, Issue 10, Pages 7841-7847

Publisher

SPRINGER
DOI: 10.1007/s13277-015-3495-y

Keywords

Melanoma progression; Osteopontin; Protein expression; Tissue microarray

Categories

Funding

  1. Hungarian National Research Fund (OTKA) [K112327]
  2. Hungarian Academy of Sciences [2011 TKI 473]
  3. European Union
  4. European Social Fund [TAMOP-4.2.4.A/2-11/1-2012-0001]
  5. State of Hungary
  6. [TAMOP-4.2.2/B-10/1-2010-0024]
  7. [TAMOP-4.2.2.A-11/1/KONV-2012-0031]

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It was shown that osteopontin (OPN), a glycophosphoprotein, plays divergent roles in cancer progression. In addition to multiple intra- and extracellular functions, it facilitates migration of tumour cells, has crucial role in cell adhesion and is associated with increased metastasis formation. In previous studies, we performed global gene expression profiling on a series of primary melanoma samples and found that OPN was significantly overexpressed in ulcerated melanomas. The major purpose of this study was to define OPN expression in primary melanomas with differing biological behaviours. OPN mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in primary melanoma tissues. Immunohistochemistry was performed using a tissue microarray. Cox regression tests were used for survival analysis. Greater than 50 % of the tissues exhibited high protein expression that was significantly associated with tumour thickness and metastasis. OPN mRNA expression was significantly increased in thicker melanomas and lesions with an ulcerated surface. Increased expression was primarily detected in advanced-stage tumours. A multivariate Cox regression analysis revealed that high OPN expression, tumour thickness and metastasis were significantly associated with reduced relapse-free survival. In summary, high OPN mRNA and protein expression were associated with a less favourable clinical outcome of primary melanoma patients. We determined that OPN is a significant predictive factor for the survival of primary melanoma patients. Based on our and others data, the high expression of OPN may have a crucial stimulatory role in tumour progression and metastasis formation, which, thus, have been proposed as potential targets for cancer diagnosis and therapy.

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