Oikonomopoulou Katerina, Scorilas Andreas, Michael Iacovos P, Grass Linda, Soosaipillai Antoninus, Rosen Barry, Murphy Joan, Diamandis Eleftherios P
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Tumour Biol. 2006;27(2):104-14. doi: 10.1159/000092325. Epub 2006 Mar 24.
Kallikreins are a family of secreted serine proteases, encoded by 15 genes which all localize in tandem on chromosome 19q13.4. Several members of this family have been previously associated with ovarian cancer. Kallikreins 6 (KLK6) and 10 (KLK10) are elevated in tumour cells, serum and ascites fluid of ovarian cancer patients and correlate with disease prognosis. Other kallikreins that have been related to ovarian cancer include KLK4, 5, 7, 8, 9, 11, 13, 14 and 15. We hypothesized that KLK6 and KLK10 can be utilized to monitor dissemination of ovarian cancer cells in blood and ascites fluid of ovarian cancer patients.
RNA was isolated by immunomagnetic separation of cancer cells and was amplified by RT-PCR.
Screening for disseminated cancer cells in blood from 24 ovarian cancer patients, with RT-PCR for KLK6 mRNA, resulted in 75% positivity; however, this was not different from the positivity of normal controls. By utilizing KLK10 as a marker, the positivity of patients was 40% versus 20% of controls. Screening of ascites fluid of ovarian cancer patients revealed 90% positivity for KLK6 and KLK10 mRNA compared with 33% for other cancer types. Significant correlations were identified among mRNA of KLK4, 5, 6, 7, 8, 9, 10, 11, 13, 14 and 15 in cancer cells isolated from ascites fluid.
Kallikrein expression by ovarian cancer cells is not specific enough for detecting disseminated disease. Kallikrein expression may have some value for differentiating ovarian cancer from other types of cancer or from non-malignant diseases that lead to ascites accumulation.
激肽释放酶是一类分泌型丝氨酸蛋白酶家族，由15个基因编码，这些基因在19号染色体q13.4上串联定位。该家族的几个成员先前已与卵巢癌相关。激肽释放酶6（KLK6）和10（KLK10）在卵巢癌患者的肿瘤细胞、血清和腹水中升高，并与疾病预后相关。其他与卵巢癌相关的激肽释放酶包括KLK4、5、7、8、9、11、13、14和15。我们假设KLK6和KLK10可用于监测卵巢癌患者血液和腹水中癌细胞的扩散。
通过癌细胞的免疫磁分离分离RNA，并通过逆转录聚合酶链反应（RT-PCR）进行扩增。
用RT-PCR检测24例卵巢癌患者血液中播散癌细胞的KLK6 mRNA，阳性率为75%；然而，这与正常对照组的阳性率没有差异。以KLK10作为标志物，患者的阳性率为40%，而对照组为20%。对卵巢癌患者腹水的筛查显示，KLK6和KLK10 mRNA的阳性率为90%，而其他癌症类型为33%。从腹水中分离的癌细胞中，KLK4、5、6、7、8、9、10、11、13、14和15的mRNA之间存在显著相关性。
卵巢癌细胞的激肽释放酶表达对于检测播散性疾病的特异性不足。激肽释放酶表达可能在区分卵巢癌与其他类型癌症或导致腹水积聚的非恶性疾病方面具有一定价值。
