Investigation of Tumor Angiogenesis in an Id Mouse Model: Role of Host-Tumor Interactions

Kreisle, Regina A.; Ershler, William B.

doi:10.1093/jnci/80.11.849

Cited by 39 publications

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“…Tumor angiogenesis was assessed as previously described (54)(55)(56). 4T1 clones (EV, R, and RL) were cultured and harvested when they were in exponential growth.…”

Section: Intradermal Tumor Angiogenesis Assaymentioning

confidence: 99%

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Venkatesha

Hanai

Seth

et al. 2006

Molecular Cancer Research

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Lipocalin 2 is an iron-binding secreted protein that converts embryonic kidney mesenchyme to epithelia. Previously, we reported that lipocalin 2 could revert 4T1-ras-transformed mesenchymal tumor cells to a more epithelial phenotype, increase E-cadherin expression, and suppress cell invasiveness in vitro and in vivo, indicating that lipocalin 2 is a metastasis suppressor. Here, we show that lipocalin 2 can suppress the ras-induced expression of vascular endothelial growth factor in 4T1 cells via down-regulation of ras mitogenactivated protein kinase and ras phosphatidylinositol-3-kinase signaling. In addition, the expression of thrombospondin-1 (an antiangiogenic molecule) was increased in tumors formed by 4T1-ras cells into which lipocalin 2 was stably introduced. Tumor angiogenesis, assessed via an intradermal tumor angiogenesis assay, was also suppressed by lipocalin 2. We also show that caveolin-1 is a critical mediator of this activity. These data provide new insights into the action of lipocalin 2 and raise the possibility that the administration of lipocalin 2 may be useful for inhibiting tumor angiogenesis, in addition to suppressing tumor metastasis, in cancers which show ras activation. (Mol Cancer Res 2006;4(11):821 -9)

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“…Tumor angiogenesis was assessed as previously described (54)(55)(56). 4T1 clones (EV, R, and RL) were cultured and harvested when they were in exponential growth.…”

Section: Intradermal Tumor Angiogenesis Assaymentioning

confidence: 99%

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Venkatesha

Hanai

Seth

et al. 2006

Molecular Cancer Research

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“…angiogenesis assay (Kreisle and Ershler, 1988). Aliquots of 10 µl of cell suspension were inoculated i.d.…”

Section: Angiogenesis Assaymentioning

confidence: 99%

Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis

1999

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Tumour cells exposed to hypoxia have been shown to up-regulate the expression of vascular endothelial growth factor (VEGF). The purpose of the present work was to investigate whether hypoxia-induced VEGF up-regulation can result in increased metastatic efficiency of human melanoma cells. Two melanoma lines, one showing high (A-07) and the other showing low (D-12) VEGF secretion under aerobic conditions, were included in the study. Cell cultures were exposed to hypoxia (oxygen concentrations < 10 ppm) in vitro and metastatic efficiency, i.e. lung colonization efficiency, as well as transplantability and angiogenic potential were assessed in BALB/c- nu/nu mice. Both cell lines showed significantly increased VEGF secretion under hypoxic conditions as measured by enzyme-linked immunosorbent assay. The D-12 cells showed increased metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. The metastatic efficiency increased with the duration of the hypoxia treatment and decreased with the time after reoxygenation. The A-07 cells on the other hand showed unchanged metastatic efficiency, transplantability and angiogenic potential following exposure to hypoxia. Both cell lines showed significantly decreased metastatic efficiency and angiogenic potential in mice treated with neutralizing antibody against VEGF. These results suggest that (a) VEGF is a limiting factor for the rate of angiogenesis in low but not in high VEGF-expressing melanomas under normoxic conditions and (b) transient hypoxia might promote the development of metastases in low VEGF-expressing melanomas by upregulating the expression of VEGF and hence enhancing the angiogenic potential of the tumour cells. © 1999 Cancer Research Campaign

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“…Angiogenic potential was assessed in vivo using the intradermal angiogenesis assay (Kreisle and Ershler, 1988;Runkel et al, 1991). Adult female BALB/c-nu/nu mice, bred at our research institute, were used as test animals.…”

Section: Angiogenesismentioning

confidence: 99%

Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma

Rofstad

Danielsen²

1998

Br J Cancer

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Summary Tumour cells exposed to hypoxia in vitro can show increased expression of several selected genes, including the gene encoding the vascular endothelial growth factor (VEGF), suggesting that hypoxia followed by reoxygenation might promote the malignant progression of tumours. An in vitro/in vivo study was conducted to investigate whether hypoxia can increase the angiogenic potential of tumour cells through increased VEGF secretion. Four human melanoma cell lines (A-07, D-12, R-18, U-25) were included in the study. Cell cultures were exposed to hypoxia (oxygen concentration <10 p.p.m.) in vitro using the steel chamber method. Rate of VEGF secretion was measured in vitro in aerobic and hypoxic cell cultures by ELISA. Angiogenesis was assessed in vivo using the intradermal angiogenesis assay. Aliquots of cells harvested from aerobic cultures or cultures exposed to hypoxia for 24 h were inoculated intradermally in the flanks of adult female BALB/cnu/nu mice. Tumours developed and angiogenesis was quantified by scoring the number of capillaries in the dermis oriented towards the tumours. The number of tumour-oriented capillaries did not differ significantly between tumours from hypoxic and aerobic cultures for A-07 and U-25, whereas tumours from hypoxic cultures showed a larger number of tumour-oriented capillaries than tumours from aerobic cultures for D-1 2 and R-1 8. The VEGF secretion under aerobic conditions and the absolute increase in VEGF secretion induced by hypoxia were lower for D-12 and R-18 than for A-07 and U-25, whereas the relative increase in VEGF secretion induced by hypoxia was higher for D-12 and R-18 than for A-07 and U-25. VEGF is not a limiting factor in the angiogenesis of some tumours under normoxic conditions. Hypoxia can increase the angiogenic potential of tumour cells by increasing the secretion of VEGF, but only of tumour cells showing low VEGF secretion under normoxia. Transient hypoxia might promote the malignant progression of tumours by temporarily increasing the angiogenic potential of tumour cells showing low VEGF expression under normoxic conditions. Keywords: angiogenesis; hypoxia; melanoma; vascularization; VEGF Many malignant tumours develop regions of hypoxic cells during growth (Coleman, 1988;Vaupel et al, 1989;Brown and Giaccia, 1994). Two types of hypoxia have been recognized: chronic hypoxia, arising from limitations in oxygen diffusion, and acute hypoxia, resulting from transient stoppages in microregional blood flow (Stone et al, 1993;Horsman, 1995). Reoxygenation of hypoxic cells occurs during unperturbed tumour growth as a result of reopening of temporarily closed vessels and during therapy as a result of therapy-induced tumour cell inactivation (Kallman, 1972;Brown, 1979;Chaplin et al, 1987). Hypoxia followed by reoxygenation might promote the malignant progression of tumours (Hill, 1990). Thus, tumour cells exposed to hypoxia in vitro can show increased expression of several selected genes, including genes encoding cell cycle-regulatory proteins, haematopoietic...

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Investigation of Tumor Angiogenesis in an Id Mouse Model: Role of Host-Tumor Interactions

Cited by 39 publications

References 0 publications

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Hypoxia-induced metastasis of human melanoma cells: involvement of vascular endothelial growth factor-mediated angiogenesis

Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma

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