Unfavorable Prognostic Value of Human Kallikrein 7 Quantified by ELISA in Ovarian Cancer Cytosols

Shan, Shannon J.C.; Scorilas, Andreas; Katsaros, Dionyssios; Longrais, Irene Rigault de la; Massobrio, M; Diamandis, Eleftherios P.

doi:10.1373/clinchem.2006.071456

Cited by 36 publications

(41 citation statements)

References 29 publications

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“…Our work (Supplementary Fig. S4; Supplementary Table S3) confirmed that increased KLK7 expression is a hallmark (15) of EOC, particularly the serous subtype and an association between high KLK7 levels with high tumor grade, chemoresistance, and shorter survival time (16)(17)(18). We showed that KLK7 directs MCA formation and chemoresistance likely by upregulating α 5 β 1 integrin pathways.…”

Section: Discussionsupporting

confidence: 76%

“…Our clinical data (Supplementary Fig. S4; Supplementary Tables S1 and S3) and a previous report showed that patients who had shorter progression-free and overall survival time after surgery had increased KLK7 expression (18). We then investigated if KLK7-expressing cells proliferate faster and how they respond to chemoreagents.…”

Section: Klk7 and α5/β1 Integrins Are Coexpressed In Serous Primary Ementioning

confidence: 91%

“…The kallikrein-related peptidase (KLK) family comprises 15 serine proteases, with several members upregulated in EOC (12)(13)(14), including KLK7 (15)(16)(17)(18)(19)(20), which is associated with poor prognosis in EOC patients (17,18). KLKs degrade ECM molecules such as fibronectin and cell adhesion proteins contributing to skin desquamation (21) as well as activate growth factors and other proteases (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma

et al. 2010

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Kallikrein-related peptidase 7 (KLK7) is upregulated in epithelial ovarian carcinoma (EOC) with high levels correlated with poor prognosis. However, the mechanisms underlying this relationship and the role of KLK7 in EOC progression are unknown. We report that two different KLK7 transcripts, KLK7-253 and KLK7-181, are simultaneously expressed in high-grade serous EOC. Multicellular aggregates (MCA), which promote cell survival and chemoresistance, were observed in SKOV-3 cells stably overexpressing KLK7-253 in particular. Importantly, these MCAs invade into a monolayer of mesothelial cells and form cancer cell foci. Blocking MCA using antibodies against KLK7 and α 5 β 1 and β 1 integrins confirmed the involvement of KLK7 and integrinregulated cell adhesion. Increased levels of α 5 /β 1 integrins and enhanced attachment to fibronectin and vitronectin, which was blocked with an anti-β 1 integrin antibody, were also observed. Finally, Western blot and immunohistochemistry showed higher KLK7 and α 5 /β 1 integrin levels in serous EOC cells from ascites and tumor samples from chemotherapy nonresponders with short postsurvival times. Additionally, both KLK7-253 and KLK7-181 clones were more resistant to paclitaxel treatment in vitro. These findings suggest a mechanism for the association of high KLK7 levels with chemoresistance and poor prognosis for serous EOC patients by promotion of peritoneal dissemination and reinvasion via increased MCA and α 5 β 1 integrin-dependent cell adhesion. Cancer Res; 70(7); 2624-33. ©2010 AACR.

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Section: Discussionsupporting

confidence: 76%

Section: Klk7 and α5/β1 Integrins Are Coexpressed In Serous Primary Ementioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma

et al. 2010

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“…For example, the following kallikreins (transcripts or proteins) are overexpressed in cancerous tissues, in comparison with normal or benign ovarian tissues, and to correlate with higher stage and grade and poor survival (in general, unfavorable prognosis) in ovarian cancer: KLK4 (20 -23), KLK5 (10, 24 -28), KLK6 (29 -39), KLK7 (5, 27, 35, 40 -42), KLK10 (26, 31, 35 -39, 43 -48), KLK11 (26,49), and KLK15 (50). On the other hand, another group of kallikreins was also found to be overexpressed in ovarian cancer but this overexpression correlated with lower stage and grade and increased patient survival (favorable prognosis) as follows: KLK8 (26,35,51), KLK9 (52), KLK11 (35,36), KLK13 (26,53), and KLK14 (40).…”

Section: Discussionmentioning

confidence: 99%

A Multiparametric Panel for Ovarian Cancer Diagnosis, Prognosis, and Response to Chemotherapy

Zheng

Katsaros

Shan

et al. 2007

Clinical Cancer Research

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Purpose: Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients. Experimental Design: Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated. Time-dependent receiver operating characteristic curves for censored survival data were used to evaluate the performance of the biomarkers. Resampling was used to validate the performance. Results: Most biomarkers effectively separated cancer from noncancer groups. A composite marker provided an area under the curve of 0.97 (95% confidence interval, 0.95-0.99) for discriminating normal and cancer groups. Univariately, hK5 and hK6 were positively associated with progression. After adjusting for clinical variables in multivariate analysis, both hK10 and hK11 significantly predicted time to progression. Increasing levels of hK13 were associated with chemotherapy response, and the predictive power of hK13 to chemotherapy response was improved by a panel of five biomarkers. Conclusions: The evidence shows that a group of kallikreins and multiparametric combinations with other biomarkers and clinical variables can significantly assist with ovarian cancer classification, prognosis, and response to platinum-based chemotherapy. In particular, we developed a multiparametric strategy for predicting ovarian cancer response to chemotherapy, comprising several biomarkers and clinical features.

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“…(8) Both KLK5 and KLK7 were reported to be overexpressed in several cancers, including ovarian, (9)(10)(11)(12)(13)(14) lung,…”

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confidence: 99%

Parallel underexpression of kallikrein 5 and kallikrein 7 mRNA in breast malignancies

Liu

Wang

et al. 2009

Cancer Science

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Kallikrein (KLK) 5 and KLK7 were reported to be overexpressed in several cancers, but underexpressed in prostate and breast cancers. However, the expression levels of KLK5 and KLK7 in benign breast tissues and metastases, and the relationship between KLK5 and KLK7, have not been reported. In addition, the value of KLK5 and KLK7 in the diagnosis and prognosis prediction of breast cancer patients is far from clear. To further determine their role and clinical significance in breast cancer and to explore the relationship between KLK5 and KLK7, the mRNA levels of KLK5 and KLK7 in normal breast tissues, benign breast tissues, primary tumors, and lymph node metastases were detected by real-time reverse transcriptionpolymerase chain reaction and microarray. The relationship between KLK5 and KLK7 expression and clinicopathological parameters, and the correlation between the mRNA levels of KLK5 and KLK7 as well as the 5′-uncoding regions of KLK5 and KLK7 were analyzed. The mRNA levels of KLK5 and KLK7 were both downregulated in breast cancers relative to normal and benign tissues, and downregulated in metastases compared to primary cancers. Underexpression of KLK5 and KLK7 was correlated with postmenopausal status and positive estrogen receptor status. The mRNA levels of KLK5 and KLK7 were positively correlated in breast malignancies. Moreover, four homologous sequences and 10 transcription factors as potential regulators were found on the control regions of both KLK5 and KLK7. Thus, KLK5 and KLK7 were underexpressed in parallel, potentially with the same regulation pathways, in breast malignancies, which might contribute to the carcinogenesis and development of breast cancer. They are potential biomarkers for breast cancer. (1) Emerging data indicate that KLKs are implicated in various human malignancies. The classical KLK gene KLK3 (also known as prostate-specific antigen) has proven to be a perfect biomarker for prostate cancer and has been used in clinical auxiliary diagnosis and prognosis prediction of prostate cancer.(2,3) Other KLK family members are overexpressed in many kinds of malignancies compared with their normal tissues, including ovarian, cervical, colorectal, gastric, lung, urinary bladder, pancreatic, and prostate cancer (KLK4, KLK11, KLK14, KLK15), but KLKs are underexpressed in breast and prostate cancers (KLK2, KLK3, KLK5, KLK6, KLK10, KLK13), renal cancer, and urinary bladder cancer.(4) KLK5 (also known as stratum corneum trypsin-like enzyme) and KLK7 (also known as stratum corneum chymotrypitc enzyme), which were originally identified from a keratinocyte cDNA library, (5)(6)(7) catalyze the degradation of intercellular cohesive structures in the outermost layer of the skin and contribute to the cell-shedding process of the skin surface, (6) which is similar to the shedding of tumor cells into the surrounding microenvironment. (8) Both KLK5 and KLK7 were reported to be overexpressed in several cancers, including ovarian, (9)(10)(11)(12)(13)(14) lung,testicular, (16,17) urinal bladder, (18) and cervi...

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Unfavorable Prognostic Value of Human Kallikrein 7 Quantified by ELISA in Ovarian Cancer Cytosols

Cited by 36 publications

References 29 publications

Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma

Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma

A Multiparametric Panel for Ovarian Cancer Diagnosis, Prognosis, and Response to Chemotherapy

Parallel underexpression of kallikrein 5 and kallikrein 7 mRNA in breast malignancies

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