Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential

Westphal, Johan R.; Hullenaar, R. G. van't; Laak, J. A. van der; Cornelissen, Ine M. H. A.; Schalkwijk, Lia; Muijen, G N van; Wesseling, Pieter; Wilde, Peter C. de; Ruiter, Dirk J.; Waal, R M de

doi:10.1038/bjc.1997.427

Cited by 57 publications

(48 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vascular densities ranging between 10 to 40 vessels /mm 2 were shown in human melanoma xenografts obtained from different cell lines, a difference that was not correlated with metastatic potential in nude mice. 34 Nonetheless, in our study, tumors from mice given angiostatin gene therapy displayed a lower vessel density, thus indicating that treatment limited tumor vasculature, a data indirectly confirmed by the increase in apoptotic index values observed in these tumors. In this study, both melanoma growth suppression and delayed tumor growth has been observed in treated mice in which angiostatin gene was delivered before the appearance of clinically detectable tumour nodules.…”

Section: Discussionsupporting

confidence: 67%

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Rodolfo

Catò²,

Soldati

et al. 2001

Cancer Gene Ther

View full text Add to dashboard Cite

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposomecoated plasmids carrying the cDNA coding for murine and human angiostatin ( CMVang and BSHang ) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome -coated plasmid carrying the lacZ gene or in untreated controls. The growth of both locally injected and controlateral uninjected tumors in mice bearing two melanoma grafts was significantly suppressed after intratumoral treatment. Tumor growth inhibition was also observed in mice treated by intraperitoneal delivery, suggesting that angiostatin gene therapy acts through a systemic effect. Both melanoma growth suppression and delay in the onset of tumor growth were observed in treated mice. PCR performed on tumors and normal tissues showed that the lipofected DNA was present in tissues from treated mice, and angiostatin expression was demonstrated by RT -PCR. Histopathological analysis of melanoma nodules revealed an increase in apoptotic cells and a reduction in vessel density in tumors from treated mice. Our results suggest that systemic, liposome -mediated administration of genes coding for antiangiogenic factors represents a promising strategy for melanoma treatment in humans. Cancer Gene Therapy ( 2001 ) 8, 491 ± 496

show abstract

Section: Discussionsupporting

confidence: 67%

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Rodolfo

Catò²,

Soldati

et al. 2001

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…Cell lines 530 and 1F6 are non-or sporadically metastasizing, whereas MV1, M14, Mel57, 1F6m, MV3 and BLM are frequently metastasizing. Of these six lines, MV3 and BLM tumours grow faster, and generate lung metastases much sooner compared to the other four cell lines (Westphal et al, 1997) (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…In the present study we investigated the expression of MMP-1, -2, -3, -9, TIMP-1 and TIMP-2 mRNA and protein in a previously described xenograft model consisting of eight human melanoma cell lines with different metastatic capacity after subcutaneous (s.c.) injection into nude mice (van Muijen et al, 1991a(van Muijen et al, , 1991bWestphal et al, 1997). We show for the first time that increased expression of activated MMP-2 is correlated with melanoma progression, indicating that activated MMP-2 may be required for melanoma invasion and metastasis.…”

mentioning

confidence: 85%

“…All cell lines were derived from surgically removed human metastases, and form local tumours after s.c. injection into nude mice. The xenografts differ in growth rate and capacity to form spontaneous lung metastases, as described previously (Westphal et al, 1997) (Table 1). Melanoma cell line M24met was kindly provided by Dr B Mueller (The Scripps Institute, La Jolla, CA, USA), and served as a positive control for MMP-1 expression.…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

See 1 more Smart Citation

Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression

et al. 1999

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumour progression and metastasis. In this study, we investigated the in vitro and in vivo expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 mRNA and protein in a previously described human melanoma xenograft model. This model consists of eight human melanoma cell lines with different metastatic behaviour after subcutaneous (s.c.) injection into nude mice. MMP-1 mRNA was detectable in all cell lines by reverse transcription polymerase chain reaction (RT-PCR), but the expression was too low to be detected by Northern blot analysis. No MMP-1 protein could be found using Western blotting. MMP-2 mRNA and protein were present in all cell lines, with the highest expression of both latent and active MMP-2 in the highest metastatic cell lines MV3 and BLM. MMP-3 mRNA was expressed in MV3 and BLM, and in the non-metastatic cell line 530, whereas MMP-3 protein was detectable only in MV3 and BLM. None of the melanoma cell lines expressed MMP-9. TIMP-1 and TIMP-2 mRNA and protein, finally, were present in all cell lines. A correlation between TIMP expression level and metastatic capacity of cell lines, however, was lacking. MMP and TIMP mRNA and protein expression levels were also studied in s.c. xenograft lesions derived from a selection of these cell lines. RT-PCR analysis revealed that MMP-1 mRNA was present in MV3 and BLM xenografts, and to a lesser extent in 530. Positive staining for MMP-1 protein was found in xenograft lesions derived from both low and high metastatic cell lines, indicating an in vivo up-regulation of MMP-1. MMP-2 mRNA was detectable only in xenografts derived from the highly metastatic cell lines 1F6m, MV3 and BLM. In agreement with the in vitro results, the highest levels of both latent and activated MMP-2 protein were observed in MV3 and BLM xenografts. With the exception of MMP-9 mRNA expression in 530 xenografts, MMP-3, MMP-9, and TIMP-1 mRNA and protein were not detectable in any xenograft, indicating a down-regulated expression of MMP-3 and TIMP-1 in vivo. TIMP-2 mRNA and protein were present in all xenografts; interestingly, the strongest immunoreactivity of tumour cells was found at the border of necrotic areas. Our study demonstrates that of all tested components of the matrix metalloproteinase system, only expression of activated MMP-2 correlates with increased malignancy in our melanoma xenograft model, corroborating an important role of MMP-2 in human melanoma invasion and metastasis. © 1999 Cancer Research Campaign

show abstract

“…Xenografting Procedures-The human melanoma cell line BLM and the stable BLM transfectants were xenografted in BALB/C nu/nu mice kept under aseptic conditions, essentially as described (11). Subconflu-* The costs of publication of this article were defrayed in part by the payment of page charges.…”

Section: Methodsmentioning

confidence: 99%

The Angiopoietin-like Factor Cornea-derived Transcript 6 Is a Putative Morphogen for Human Cornea

Peek¹,

Kammerer²,

Frank³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human cornea-specific protein cornea-derived transcript 6 (CDT6) is a member of the angiopoietin gene family. We report the structural and functional characterization of CDT6. We demonstrate that CDT6 is a secreted protein that folds into disulfide-linked homotetramers by coiled-coil interactions. The finding that CDT6 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesis. To test this hypothesis and to assay the effect of the protein on a growing tissue with high vascular density, CDT6 was expressed in a mouse xenograft model. Expression of CDT6 led to a reduction in tumor growth and aberrant blood vessel formation by inducing massive fibrosis. Interestingly, expression of CDT6 also resulted in the deposition of extracellular matrix components typical for the mature corneal stromal layer. These observations strongly suggest a role as morphogen for CDT6 in inducing a corneal phenotype in vivo.

show abstract

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential

Cited by 57 publications

References 25 publications

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression

The Angiopoietin-like Factor Cornea-derived Transcript 6 Is a Putative Morphogen for Human Cornea

Contact Info

Product

Resources

About