Roles of osteopontin and matrix metalloproteinase-7 in occurrence, progression, and prognosis of nonsmall cell lung cancer

Sun, Ying; Li, Dan; Lv, Xiaoyi; Hua, Shucheng; Han, Jichang; Xu, Feng; Li, Xiandong

doi:10.4103/1735-1995.172980

Cited by 11 publications

(3 citation statements)

References 29 publications

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“…Furthermore, MMP-2 localized to the tumors cells along the luminal surface of the cyst wall, suggesting additional roles for MMPs in the development of cysts in VS (41). Our immunofluorescence and cytokine analysis of cyst fluid did not incorporate MMPs; however, osteopontin was upregulated in cyst fluid and CSF and is known to be a substrate of several MMPs, including MMP-2 (42–45). Furthermore, MCP-1 is known to stimulate the expression of multiple MMPs in various cell types, including cancer (46–49).…”

Section: Discussionmentioning

confidence: 80%

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma

Nisenbaum,

Wiefels,

Telischi

et al. 2023

Otol Neurotol

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Background The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. Hypothesis Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. Methods Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80+ M1 and CD163+ M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. Results Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein (p = 0.0020), particularly MCP-1 (p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80+ staining in VS tissue (r = 0.8852; p = 0.0015) but not CD163+ staining. Conclusion Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80+ M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention.

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Section: Discussionmentioning

confidence: 80%

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma

Nisenbaum,

Wiefels,

Telischi

et al. 2023

Otol Neurotol

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“…There are conflicting reports regarding the association between osteopontin expression and grading. Marcil et al (2009) and Rud et al (2012) found a positive correlation between given factors, whereas Boldrini et al (2005) and Donati et al (2005) found this correlation negative [ 19 , 25 – 29 ].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer

et al. 2020

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IntroductionTriple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases.Material and methodsThe immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies.ResultsAll patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes.ConclusionsThere is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

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“…Expression patterns of OPN and MMP-3 were overlapped in the stroma during skin incisional wound healing [61] and those of OPN and MMP-7 were overlapped during involution of the postpartum uterus [62] in mice experiments. Higher expressions of OPN and MMP-7 are closely associated with the occurrence, progression, and prognosis of non-small cell lung cancer (NSCLC) [63].…”

Section: Binding Specificities and Functions Of Mmp-cleaved Opnmentioning

confidence: 99%

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

et al. 2021

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Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.

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Roles of osteopontin and matrix metalloproteinase-7 in occurrence, progression, and prognosis of nonsmall cell lung cancer

Cited by 11 publications

References 29 publications

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma

Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

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