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Elevated hyaluronan and hyaluronan-mediated motility receptor are associated with biochemical failure in patients with intermediate-grade prostate tumorsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Rizzardi A.E., Vogel R.I., Koopmeiners J.S., Forster C.L., Marston L.O., Rosener N.K., Akentieva N., Price M.A., Metzger G.J., Warlick C.A., Henriksen J.C., Turley E.A., McCarthy J.B., Schmechel S.C.
- Журнал: Cancer
- Том: 120
- Номер: 12
- Год издания: 2014
- Издательство: John Wiley & Sons Inc.
- Местоположение издательства: United States
- Первая страница: 1800
- Последняя страница: 1809
- Аннотация: Background—The clinical course of prostate cancer (PCa) measured by biochemical failure(BF) after prostatectomy remains unpredictable in many patients, particularly in intermediateGleason score (GS) 7 tumors, suggesting that identification of molecular mechanisms associatedwith aggressive PCa biology may be exploited for improved prognostication or therapy.Hyaluronan (HA) is a high molecular weight polyanionic carbohydrate produced by synthases(HAS1-3) and fragmented by oxidative/nitrosative stress and hyaluronidases (HYAL1-4, SPAM1)common in PCa microenvironments. HA and HA fragments interact with receptors CD44 andHMMR resulting in increased tumor aggressiveness in experimental PCa models. We evaluatedthe association of HA-related molecules with BF after prostatectomy in GS7 tumors.Methods—Tissue microarrays were constructed from a 96-patient cohort. HA histochemistry andHAS2, HYAL1, CD44, CD44v6, and HMMR immunohistochemistry were quantified usingdigital pathology techniques.Results—HA in tumor-associated stroma and HMMR in malignant epithelium were significantlyand marginally significantly associated with time to BF in univariate analysis, respectively. Afteradjusting for clinicopathologic features, both HA in tumor-associated stroma and HMMR inmalignant epithelium were significantly associated with time to BF. Although not significantlyassociated with BF, HAS2 and HYAL1 positively correlated with HMMR in malignantepithelium. Cell culture assays demonstrated that HMMR bound native and fragmented HA,promoted HA uptake, and was required for a pro-migratory response to fragmented HA.Conclusions—HA and HMMR are factors associated with time to BF in GS7 tumors,suggesting that increased HA synthesis and fragmentation within the tumor microenvironmentstimulates aggressive PCa behavior through HA-HMMR signaling.
- Добавил в систему: Акентьева Наталья Павловна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | Cancer_Akentieva.pdf | 1,9 МБ | 1 июня 2022 [Akentieva] |