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Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model.

Davies MM, Mathur P, Carnochan P, Saini S, Allen-Mersh TG - Br. J. Cancer (2002)

Bottom Line: We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis.Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls.Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgery, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.

ABSTRACT
One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.

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There was a significant increase (M.W.U. P=0.04) in the PCNA index in subcutaneous K12/TR tumours infused systemically with bFGF compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (above). There was no significant increase (M.W.U. P=0.08) in the tumour volume of systemic bFGF infused subcutaneous K12/TR tumours compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (below).
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fig6: There was a significant increase (M.W.U. P=0.04) in the PCNA index in subcutaneous K12/TR tumours infused systemically with bFGF compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (above). There was no significant increase (M.W.U. P=0.08) in the tumour volume of systemic bFGF infused subcutaneous K12/TR tumours compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (below).

Mentions: There was a significant increase in PCNA index (P=0.04) in the bFGF (median 13.6%, iqr 10.4–16.0%) compared with the saline-infused (5%, 4.0–6.0%) group. There was a trend that did not reach statistical significance (P=0.08), for an increase in tumour volume of bFGF compared with saline-infused tumours (Figure 6Figure 6


Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model.

Davies MM, Mathur P, Carnochan P, Saini S, Allen-Mersh TG - Br. J. Cancer (2002)

There was a significant increase (M.W.U. P=0.04) in the PCNA index in subcutaneous K12/TR tumours infused systemically with bFGF compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (above). There was no significant increase (M.W.U. P=0.08) in the tumour volume of systemic bFGF infused subcutaneous K12/TR tumours compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (below).
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Related In: Results  -  Collection

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fig6: There was a significant increase (M.W.U. P=0.04) in the PCNA index in subcutaneous K12/TR tumours infused systemically with bFGF compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (above). There was no significant increase (M.W.U. P=0.08) in the tumour volume of systemic bFGF infused subcutaneous K12/TR tumours compared with controls (•: saline n=5; ○: bFGF n=5; median and interquartile range) (below).
Mentions: There was a significant increase in PCNA index (P=0.04) in the bFGF (median 13.6%, iqr 10.4–16.0%) compared with the saline-infused (5%, 4.0–6.0%) group. There was a trend that did not reach statistical significance (P=0.08), for an increase in tumour volume of bFGF compared with saline-infused tumours (Figure 6Figure 6

Bottom Line: We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis.Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls.Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgery, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.

ABSTRACT
One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.

Show MeSH
Related in: MedlinePlus