5653

KLK6

kallikrein-related peptidase 6;KLK6;kallikrein-related peptidase 6

kallikrein-6|neurosin|protease M|serine protease 18|serine protease 9|zyme

19q13.3

protein-coding

AIM: To investigate the expression of KLK6 protein and mRNA in primary breast carcinoma, and to evaluate its clinical significance in clinicopathological status of patients with primary breast carcinoma. METHODS: 88 patients with primary breast carcinoma chosen randomly were examined for KLK6 protein and mRNA expression by SABC immunohistochemistry and RT-PCR, respectively. The association of KLK6 with the clinicopathologic features of the primary breast cancer was also analysis. RESULTS: The positive expression rates of KLK6 protein in breast carcinoma tissues were 78.40% (69/88). Clinicopathological parameters of breast carcinoma were associated with KLK6 protein expression. KLK6 protein was expressed less frequently in breast carcinoma tissues with lymph nodes metastasis (P<0.01) and ER(+) (P<0.05). Additionally, the mean expression level of KLK6 mRNA in cancerous tissues was significantly higher than that in normal tissues (P<0.01). However, KLK6 mRNA expression was negatively correlated with metastasis (P<0.01) and ER status (P<0.01). The expression of KLK6 protein and mRNA in primary breast carcinoma tissues was not associated with that of CerbB-2. CONCLUSION: KLK6 expression in cancerous tissues may play an important role in the invasion and metastasis of primary breast carcinoma. The detection of it along with clinical staging may help to predict the prognosis of patients with primary breast carcinoma.

Human kallikrein 6 (hK6), a trypsin-like serine protease, is a newly identified member of the kallikrein gene family. Its involvement in inflammatory CNS lesions and in demyelination has been reported. Recent work has suggested that expression of this enzyme is significantly elevated in patients with ovarian cancer. We have identified many tumour cell lines that secrete hK6, but its physiological role is unknown. Here, we try to unveil the role of this kallikrein in the metastasis and invasion of tumour cells. We demonstrate that purified human recombinant hK6 can cleave gelatin in zymography and can efficiently degrade high-molecular-weight extracellular matrix proteins such as fibronectin, laminin, vitronectin and collagen. In Boyden chamber assays, we found that tumour cells treated with a neutralizing hK6 antibody migrate less than control cells. We conclude that hK6 might play a role in the invasion and metastasis of tumour cells and may be a candidate therapeutic target.

OBJECTIVE: To approach the relationship between the expression of hK6 in ovarian neoplasm and clinicopathological variables and prognosis in ovarian cancer patients for finding a new tumor marker of the ovarian cancer. METHODS: The expression of hK6 was detected by immunohistochemistry in 19 cases of benign, 11 cases of borderline and 45 cases of malignant ovarian neoplasms and statistically analyzed whether its expression correlate with clinicopathological variables and prognosis in patients with ovarian cancer. RESULTS: The expression of hK6 in ovarian cancer tissues (60.0%) was significantly higher than that in the benign (15.8%) and borderline (27.3%) ovarian neoplasm tissues (P < 0.01). The expression of hK6 in higher-grade ovarian cancer tissues (68.4% ) was higher than that in low-grade ones (14.3%, P < 0.05). The expression of hK6 in late-stage (stage III, 76.7%) was significantly higher than that in early-stage (stage I or II, 26.7%, P < 0.01). The expression of hK6 was significantly higher in patients with lymph node metastasis (77.8%) than that in patients without (33.3%, P < 0.01). The expression of hK6 in the cancer tissues in the patients died, or with reccurence or metastasis within 3 years after surgery was higher (75.0%) than that in the patients with stable disease (42.9%, P < 0.05). CONCLUSION: The expression of hK6 in ovarian cancer was higher than that in benign and borderline ovarian neoplasms. The expression of hK6 is higher in the ovarian cancer of late stage, higher-grade, with lymph node metastasis and is associated with a poorer prognosis. hK6 may become a new markers in prediction of prognosis of the patients with ovarian tumors.