Host-derived osteopontin maintains an acute inflammatory response to suppress early progression of extrinsic cancer cells

• Published in: International journal of cancer Vol. 131; no. 2; pp. 322 - 333
• Main Authors: Hsieh, Yu-Hua, Margaret Juliana, M., Ho, Kang-Jey, Kuo, Hui-Chien, van der Heyde, Henri, Elmets, Craig, Chang, Pi-Ling
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.07.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: acute inflammation; Animals; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cells; cutaneous squamous cell carcinoma cell line; Dermatology; Disease Progression; early cancer cell progression; Female; host-derived osteopontin; Inflammation; Medical research; Medical sciences; Mice; Mice, Transgenic; Osteopontin - blood; Osteopontin - physiology; Proteins; Rodents; Tumor Microenvironment; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Skin disease; acute inflammation; cutaneous squamous cell carcinoma cell line; Acute; Cell microenvironment; Osteopontin; Inflammation; host-derived osteopontin; Malignant tumor; Skin cancer; Skin squamous cell carcinoma; Cancerology; early cancer cell progression; Established cell line; Tumor progression; Early; tumor microenvironment; Tumor cell; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.26359

The matricellular protein osteopontin (OPN), expressed in various cancer types and elevated in the blood of cancer patients, is thought to have different functions when derived from host versus cancer cells. To assess the effect of host‐derived OPN on growth of cancers of epithelial origin, we established a line of cutaneous squamous cell carcinoma (SCC) cells, named ONSC, which lacks the OPN gene and develops SCC in syngeneic wild‐type (WT) and OPN‐null mice. At 8 and/or 10 week after subcutaneous injection of ONSC cells in mice, however, there was a lower tumor incidence in WT mice, suggesting that host‐derived OPN is associated with suppression of early growth of extrinsic cancer cells. Histological, immunohistochemical, biochemical and hematological analyses were performed on the tumor microenvironment and blood from tumor‐bearing mice during the first week after implantation. Host‐derived OPN suppression of extrinsic ONSC cell progression is likely mediated through elicitation of an early innate inflammatory response, through its function as a chemoattractant and/or by enhancing survival of inflammatory cells. Further, consistent with a previous report, the serum levels of host‐derived OPN, which are elevated during the early phase of tumor growth in mice implanted with ONSC, appear to reflect an anti‐tumor progression effect.