The significance of lumican expression in ovarian cancer drug-resistant cell lines

被引:25
|
作者
Klejewski, Andrzej [1 ,2 ]
Sterzynska, Karolina [3 ]
Wojtowicz, Karolina [3 ]
Swierczewska, Monika [3 ]
Partyka, Malgorzata [3 ]
Brazert, Maciej [4 ]
Nowicki, Michal [3 ]
Zabel, Maciej [3 ,5 ]
Januchowski, Radoslaw [3 ]
机构
[1] Poznan Univ Med Sci, Dept Nursing, Poznan, Poland
[2] Poznan Univ Med Sci, Dept Obstet & Womens Dis, Poznan, Poland
[3] Poznan Univ Med Sci, Dept Histol & Embryol, Poznan, Poland
[4] Poznan Univ Med Sci, Div Infertil & Reprod Endocrinol, Dept Gynecol Obstet & Gynecol Oncol, Poznan, Poland
[5] Wroclaw Med Univ, Dept Histol & Embryol, Wroclaw, Poland
关键词
drug resistance; ovarian cancer; lumican; collagen; EXTRACELLULAR-MATRIX PROTEINS; PEGYLATED LIPOSOMAL DOXORUBICIN; HUMAN PANCREATIC-CANCER; CISPLATIN-RESISTANCE; MULTIDRUG-RESISTANCE; ANTICANCER DRUGS; CARCINOMA; GENE; MICROENVIRONMENT; PROTEOGLYCAN;
D O I
10.18632/oncotarget.20169
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: The aim of the present study is to determine the expression of LUM in drug-resistant ovarian cancer cell lines. Methods: Doxorubicin-(DOX), topotecan-(TOP) and vincristine-(VIN) resistant variants of the W1 ovarian cancer cell line were used in this study. We used quantitative real-time polymerase chain reactions to determine LUM mRNA levels. Protein expression was detected using Western blot and immunocytochemistry assays. Protein glycosylation was investigated using PGNase F digestion. Immunohistochemistry assays were used to determine protein expression in ovarian cancer patients. Results: We observed increased expression of LUM in drug-resistant cell lines at both the mRNA and the protein level. The most abundant LUM expression was observed in TOP-resistant cell line. We observed LUM bands that corresponded to different molecular masses, and the most abundant LUM form was the secreted form, which had a mass of 50 kDa. Double immunofluorescence analysis showed coexpression of LUM and COL3A1 as well as the presence of extracellular COL3A1 in the TOP-resistant cell line. Finally, we detected the LUM protein in ovarian cancer tissue. Conclusion: The expression of LUM in cytostatic-resistant cell lines suggests its role in drug resistance. The co-expression of LUM and COL3A1 indicates the significance of LUM in collagen fibre assembly. Expression in ovarian cancer tissue suggests that LUM can play a role in ovarian cancer pathogenesis in ways similar to other cancers.
引用
收藏
页码:74466 / 74478
页数:13
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