Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment

Alahuhta, Ilkka; Aikio, Mari; Väyrynen, Otto; Nurmenniemi, Sini; Suojanen, Juho; Teppo, Susanna; Pihlajaniemi, Taina; Heljasvaara, Ritva; Salo, Tuula; Nyberg, Pia

doi:10.1016/j.yexcr.2015.06.012

Cited by 18 publications

(19 citation statements)

References 43 publications

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“…In vitro studies have shown that in an appropriate concentration range, collagen XVIII-derived endostatin suppresses the migration and invasion of head, neck and tongue SCC cells (17,32). However, our recently published data show that overexpression of endostatin in tongue SCC cells inhibits invasion but increases the proliferation, and results in larger tumors when transplanted into the subcutis of nude mice (33).…”

Section: Discussionmentioning

confidence: 94%

Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels

Karppinen

Honkanen

Heljasvaara

et al. 2016

Experimental Dermatology

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As the second most common skin malignancy, cutaneous squamous cell carcinoma (cSCC) is an increasing health concern, while its pathogenesis at molecular level remains largely unknown. We studied the expression and localisation of two homologous basement membrane (BM) collagens, types XV and XVIII, at different stages of cSCC. These collagens are involved in angiogenesis and tumorigenesis, but their role in cancer development is incompletely understood. Quantitative RT-PCR analysis revealed upregulation of collagen XVIII, but not collagen XV, in primary cSCC cells in comparison with normal human epidermal keratinocytes. In addition, the Ha-ras-transformed invasive cell line II-4 expressed high levels of collagen XVIII mRNA, indicating upregulation in the course of malignant transformation. Immunohistochemical analyses of a large human tissue microarray material showed that collagen XVIII is expressed by tumor cells from grade 1 onwards, while keratinocytes in normal skin and in premalignant lesions showed negative staining for it. Collagen XV appeared instead as deposits in the tumor stroma. Our findings in human cSCCs and in mouse cSCCs from the DMBA-TPA skin carcinogenesis model showed that collagen XVIII, but not collagen XV or the BM markers collagen IV or laminin, was selectively reduced in the tumor vasculature, and this decrease associated significantly with cancer progression. Our results demonstrate that collagens XV and XVIII are expressed in different sites of cSCC and may contribute in a distinct manner to processes related to cSCC tumorigenesis, identifying these collagens as potential biomarkers in the disease.

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Section: Discussionmentioning

confidence: 94%

Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels

Karppinen

Honkanen

Heljasvaara

et al. 2016

Experimental Dermatology

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“…The described organotypic leiomyoma 3D solid disc model utilizes human tissue material with authentic components of the tumour microenvironment (TME) such as fibroblasts, insoluble and soluble ECM components, and a complex tumour tissue architecture including nerves and vessels [3,4,5]. Although cells in the myoma discs are not viable, their presence is important as they simulate the in vivo tumour cellular environment [6]. Additionally, myoma discs are hypoxic providing natural surroundings for cancer cells in vitro [3].…”

Section: Extracellular Matrix (Ecm) Protein Mixtures Of Non-human Orimentioning

confidence: 99%

“…Measure the invasion depths for three separate invasive particles with the deepest/furthest invasion. 6. Handling the results: The results can be copied from the Summary and Results windows straight into an excel-file.…”

Section: Measuring the Depth Of Invasion Adjust The Settings For Thementioning

confidence: 99%

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Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Åström

Heljasvaara

Nyberg

et al. 2018

Methods in Molecular Biology

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Here we describe a protocol to utilize human benign leiomyoma tissue in in vitro 3D model that enables an assessment of cell invasion. The chapter also describes detailed instructions for image analysis to quantify the results. Leiomyoma is a benign tumor of the uterus which mimics authentic components of the tumor microenvironment including fibroblasts, vessels, collagen fibers, and extracellular protein composition. The leiomyoma invasion model represents a superior 3D model for cell invasion studies compared to the other non-human organotypic models.

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“…As one of endogenous inhibitor, endostatin was found in epithelioid hemangioendothelioma (26). By its regulation to angiogenesis gene, endostatin can inhibit proliferation, migration or invasion and apoptosis of endothelial cells, to play antineoplastic activity (27).…”

Section: Discussionmentioning

confidence: 99%

Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma

et al. 2017

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Abstract.Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-17, interferon (IFN)-γ and hypoxia inducible factor (HIF)-1α, following endostatin therapy. It was demonstrated that the growth and angiogenesis of tumors were markedly suppressed by treatment with endostatin, compared with control group. The microvessel density in mice treated with endostatin was significantly inhibited in a dose-dependent manner. The expression levels of VEGF, IL-6 and IL-17 in tumors were decreased, however IFN-γ and HIF-1α expression levels were increased, following treatment with endostatin. In addition, the proportion of myeloid derived suppressor cells and tumor associated macrophages (TAMs; M2 type) were significantly decreased, whereas those of mature dendritic cells and TAMs (M1 type) were increased, and cluster of differentiation (CD)8 + T cells were recruited to infiltrate the tumors following treatment with endostatin. In addition, the expression levels of IL-6, IL-10, tumor growth factor-β and IL-17 in tumor tissue were potently decreased with endostatin therapy. These results indicated that endostatin efficiently inhibited tumor angiogenesis and reversed the immunosuppressive microenvironment associated with the presence of tumors.

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Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment

Cited by 18 publications

References 43 publications

Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels

Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels

Human Tumor Tissue-Based 3D In Vitro Invasion Assays

Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma

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