Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice

Vasiljeva, Olga; Коровин, М. С.; Gajda, Mieczysław; Brodoefel, Harald; Bojić, Lea; Krüger, Achim; Schurigt, Uta; Sevenich, Lisa; Turk, Boris; Peters, Christoph; Reinheckel, Thomas

doi:10.1038/onc.2008.59

Cited by 107 publications

(79 citation statements)

References 35 publications

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“…Our in vivo experiments indicated that tumor volume and weight were significantly reduced by suppression of Cathepsin B. This finding is consistent with a recent study of Cathepsin B in breast cancer (29). We also demonstrated lower proliferation indexes (Ki-67 and PCNA) in xenograft tumor tissues from the Cathepsin B knockdown group.…”

Section: Discussionsupporting

confidence: 81%

Silencing of Cathepsin B suppresses the proliferation and invasion of endometrial cancer

et al. 2013

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Abstract. The molecular mechanism involved in the metastasis of endometrial cancer (EC) remains unclear. The lysosomal cysteine protease Cathepsin B has been implicated in the progression of various human tumors. In the present study, we assessed the expression of Cathepsin B and its functions in EC. Immunohistochemistry was used to examine Cathepsin B expression in 76 paraffin-embedded endometrial tumor tissues. Lentiviral packing short hairpin RNA (shRNA) was transfected into HEC-1A cells to build a stable Cathepsin B knockdown cell line. The cellular levels of Cathepsin B mRNA and protein were detected by real-time PCR and western immunoblotting. The functions of Cathepsin B in EC cells were measured by MTT, migration and invasion assays. In additon, tumorigenicity assays were established in nude mice to study tumor growth in vivo. The results of our study showed that Cathepsin B was overexpressed in EC tissues compared with normal endometrium and endometrial atypical hyperplasia. Depletion of Cathepsin B in vitro inhibited cell proliferation, migration and invasion. Tumor formation assays confirmed that suppression of Cathepsin B inhibited the proliferation potential of HEC-1A cells in vivo, demonstrated by lower proliferation rates. These results suggest that Cathepsin B may act as an oncogene in EC, with the potential to provide a new therapeutic target for treating endometrial malignancy.

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Section: Discussionsupporting

confidence: 81%

Silencing of Cathepsin B suppresses the proliferation and invasion of endometrial cancer

et al. 2013

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“…Histopathological grading of hematoxylin and eosin (HE)-stained tumor sections of left thoracic mammary glands was performed in a blinded setting by an experienced histopathologist as described previously (27). For histomorphometric analysis, the area and number of metastatic foci on lung sections was measured using Axiovision LE 4.4 software (Zeiss, Oberkochen, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Preparation of PyMT Cells with Inducible CTSL ExpressionPrimary cells were prepared from tumors of MMTV-PyMT mice by mechanical disruption and enzymatic digestion of the tissue as previously described (27). Cells were spontaneously immortalized by repeated passaging for at least 25 passages.…”

Section: Methodsmentioning

confidence: 99%

Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression

Tholen

Wolanski

Stolze

et al. 2015

Journal of Biological Chemistry

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Background: Translational regulation might underlie the high expression levels of the protease cathepsin L (CTSL) associated with poor breast cancer prognosis. Results: Translation of CTSL mRNA is highly stress-resistant and promotes metastasis of murine breast cancer. Conclusion: CTSL mRNA circumvents translational shutdown in cancer-associated stress conditions. Significance: High expression of a metastasis promoting protease is maintained by translational regulation.

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“…To investigate the impact of different Ctsb and Ctsz genotypes on tumor grade, we classified premalignant and malignant lesions in a genotype-blinded fashion into the following defined histopathologic stages: atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, further subdivided into grades GI-GIII with regard to mitotic activity and cellular differentiation (31,32) (Fig. 2D).…”

Section: Progression and Histopathology Of Pymt-induced Mammarymentioning

confidence: 99%

Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice

Sevenich

Schurigt

Sachse

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

153

122

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The lysosomal cysteine proteases cathepsin B (Ctsb) and cathepsin Z (Ctsz, also called cathepsin X/P) have been implicated in cancer pathogenesis. Compensation of Ctsb by Ctsz in Ctsb −/− mice has been suggested. To further define the functional interplay of these proteases in the context of cancer, we generated Ctsz null mice, crossed them with Ctsb-deficient mice harboring a transgene for the mammary duct–specific expression of polyoma middle T oncogene (PymT), and analyzed the effects of single and combined Ctsb and Ctsz deficiencies on breast cancer progression. Single Ctsb deficiency resulted in delayed detection of first tumors and reduced tumor burden, whereas Ctsz-deficient mice had only a prolonged tumor-free period. However, only a trend toward reduced metastatic burden without statistical significance was detected in both single mutants. Strikingly, combined loss of Ctsb and Ctsz led to additive effects, resulting in significant and prominent delay of early and advanced tumor development, improved histopathologic tumor grading, as well as a 70% reduction in the number of lung metastases and an 80% reduction in the size of these metastases. We conclude that the double deficiency of Ctsb and Ctsz exerts significant synergistic anticancer effects, whereas the single deficiencies demonstrate at least partial reciprocal compensation.

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Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice

Cited by 107 publications

References 35 publications

Silencing of Cathepsin B suppresses the proliferation and invasion of endometrial cancer

Silencing of Cathepsin B suppresses the proliferation and invasion of endometrial cancer

Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression

Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice

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