Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma

Osteopontin (OPN) is a phosphoprotein with diverse functions in various physiological and pathological processes. OPN expression is increased in multiple cancers, and OPN within tumour tissue has been shown to promote key stages of cancer development. OPN levels are also elevated in the circulation...

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Main Authors: Rafael Saup, Nidhi Nair, Jingyi Shen, Anja Schmaus, Wilko Thiele, Boyan K. Garvalov, Jonathan P. Sleeman
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/4/1038
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author Rafael Saup
Nidhi Nair
Jingyi Shen
Anja Schmaus
Wilko Thiele
Boyan K. Garvalov
Jonathan P. Sleeman
author_facet Rafael Saup
Nidhi Nair
Jingyi Shen
Anja Schmaus
Wilko Thiele
Boyan K. Garvalov
Jonathan P. Sleeman
author_sort Rafael Saup
collection DOAJ
description Osteopontin (OPN) is a phosphoprotein with diverse functions in various physiological and pathological processes. OPN expression is increased in multiple cancers, and OPN within tumour tissue has been shown to promote key stages of cancer development. OPN levels are also elevated in the circulation of cancer patients, which in some cases has been correlated with enhanced metastatic propensity and poor prognosis. However, the precise impact of circulating OPN (cOPN) on tumour growth and progression remains insufficiently understood. To examine the role of cOPN, we used a melanoma model, in which we stably increased the levels of cOPN through adeno-associated virus-mediated transduction. We found that increased cOPN promoted the growth of primary tumours, but did not significantly alter the spontaneous metastasis of melanoma cells to the lymph nodes or lungs, despite an increase in the expression of multiple factors linked to tumour progression. To assess whether cOPN has a role at later stages of metastasis formation, we employed an experimental metastasis model, but again could not detect any increase in pulmonary metastasis in animals with elevated levels of cOPN. These results demonstrate that increased levels of OPN in the circulation play distinct roles during different stages of melanoma progression.
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spelling doaj.art-f4bf4a5a3ad9494086b9d7b7876709332023-11-17T18:25:39ZengMDPI AGBiomedicines2227-90592023-03-01114103810.3390/biomedicines11041038Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in MelanomaRafael Saup0Nidhi Nair1Jingyi Shen2Anja Schmaus3Wilko Thiele4Boyan K. Garvalov5Jonathan P. Sleeman6European Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyEuropean Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, GermanyOsteopontin (OPN) is a phosphoprotein with diverse functions in various physiological and pathological processes. OPN expression is increased in multiple cancers, and OPN within tumour tissue has been shown to promote key stages of cancer development. OPN levels are also elevated in the circulation of cancer patients, which in some cases has been correlated with enhanced metastatic propensity and poor prognosis. However, the precise impact of circulating OPN (cOPN) on tumour growth and progression remains insufficiently understood. To examine the role of cOPN, we used a melanoma model, in which we stably increased the levels of cOPN through adeno-associated virus-mediated transduction. We found that increased cOPN promoted the growth of primary tumours, but did not significantly alter the spontaneous metastasis of melanoma cells to the lymph nodes or lungs, despite an increase in the expression of multiple factors linked to tumour progression. To assess whether cOPN has a role at later stages of metastasis formation, we employed an experimental metastasis model, but again could not detect any increase in pulmonary metastasis in animals with elevated levels of cOPN. These results demonstrate that increased levels of OPN in the circulation play distinct roles during different stages of melanoma progression.https://www.mdpi.com/2227-9059/11/4/1038osteopontincirculating levelsmelanomatumour growthmetastasis
spellingShingle Rafael Saup
Nidhi Nair
Jingyi Shen
Anja Schmaus
Wilko Thiele
Boyan K. Garvalov
Jonathan P. Sleeman
Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
Biomedicines
osteopontin
circulating levels
melanoma
tumour growth
metastasis
title Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
title_full Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
title_fullStr Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
title_full_unstemmed Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
title_short Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma
title_sort increased circulating osteopontin levels promote primary tumour growth but do not induce metastasis in melanoma
topic osteopontin
circulating levels
melanoma
tumour growth
metastasis
url https://www.mdpi.com/2227-9059/11/4/1038
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