Thrombin cleavage of osteopontin initiates osteopontin's tumor-promoting activity.

ABSTRACT:

Background

Osteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α₄ β₁ and α₉ β₁ integrins.

Methods

Thrombin cleavage-resistant OPN_R153A knock-in (OPN-KI) mice were generated and compared to OPN deficient mice (OPN-KO) and wild type (WT) mice in their ability to support growth of melanoma cells. Flow cytometry was used to analyze tumor infiltrating leukocytes.

Results

OPN-KI mice engineered with a thrombin cleavage-resistant OPN had reduced B16 melanoma growth and fewer pulmonary metastases than WT mice. The tumor suppression phenotype of t

SUBMITTER: Peraramelli S 

PROVIDER: S-EPMC9289821 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature