Inhibition of Hyaluronan Synthase-3 Decreases Subcutaneous Colon Cancer Growth in Mice
PURPOSE:Hyaluronan and hyaluronan synthases have been implicated in cancer progression. Hyaluronan synthase-3 is up-regulated in metastatic colon cancer cells (SW620), and its expression mediates cellular growth in vitro. We hypothesized that inhibition of hyaluronan synthase-3 would decrease tumor...
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Veröffentlicht in: | Diseases of the colon & rectum 2010-04, Vol.53 (4), p.475-482 |
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Sprache: | eng |
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Zusammenfassung: | PURPOSE:Hyaluronan and hyaluronan synthases have been implicated in cancer progression. Hyaluronan synthase-3 is up-regulated in metastatic colon cancer cells (SW620), and its expression mediates cellular growth in vitro. We hypothesized that inhibition of hyaluronan synthase-3 would decrease tumor formation and/or alter the pattern of metastasis in mouse models of colon cancer growth.
METHODS:Hyaluronan synthase-3 was inhibited in SW620 cells by transfection with small interfering RNA (silenced cells); a scrambled sequence served as a negative control. To study primary tumor growth, transfected cells were injected into the flanks of BALB/c nude mice. To study metastasis, an orthotopic model was used. Metastases were confirmed histologically. Student t test and Fisher exact probability test were used for statistical analysis.
RESULTS:Inhibition of hyaluronan synthase-3 significantly decreased subcutaneous tumor growth; tumor weight was 0.94 ± 0.17 g in the hyaluronan synthase-3–silenced group vs 1.70 ± 0.26 g in the control scrambled group (P < .01). In contrast, metastases were similar in both groupsliver metastases were present in 22% of the silenced group vs 11% of the scrambled group; lung metastases were present in 6% of the silenced group vs 0% of the scrambled group (P = not significant).
CONCLUSION:Inhibition of hyaluronan synthase-3 expression in SW620 colon cancer cells decreases subcutaneous tumor growth in mice, but has less of an effect on lung and liver metastases. This observation suggests that hyaluronan synthase-3 may enhance primary colon cancer growth. |
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ISSN: | 0012-3706 1530-0358 |
DOI: | 10.1007/DCR.0b013e3181c87084 |