Inhibition of hyaluronan synthase-3 decreases subcutaneous colon cancer growth in mice

Eric Lai, Rahul Singh, Brian Teng, Yali Zhao, Elizabeth Sharratt, Gillian Howell, Ashwani Rajput, Kelli Bullard Dunn

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 ttest 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 groups: liver 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.

Original languageEnglish (US)
Pages (from-to)475-482
Number of pages8
JournalDiseases of the Colon and Rectum
Volume53
Issue number4
DOIs
Publication statusPublished - Apr 1 2010

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Keywords

  • Colon cancer
  • Hyaluronan
  • Hyaluronan synthase

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lai, E., Singh, R., Teng, B., Zhao, Y., Sharratt, E., Howell, G., ... Dunn, K. B. (2010). Inhibition of hyaluronan synthase-3 decreases subcutaneous colon cancer growth in mice. Diseases of the Colon and Rectum, 53(4), 475-482. https://doi.org/10.1007/dcr.0b013e3181c87084