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Investigating Biomarkers for Early Detection of Ovarian Cancer

 The Female Reproductive System

The female reproductive system produces the female gametes, or germ cells, called eggs. Once fertilized by a sperm cell, the male gamete, the resultant zygote develops into a fetus during gestation. Human females are born with their lifetime supply of eggs, which are housed in the two ovaries. Once per month, one of these eggs matures and is released from the ovary into the associated fallopian tube. There are two fallopian tubes in the female reproductive system, each connecting one ovary to the uterus, or womb. Once the egg reaches the uterus, it can be fertilized and pregnancy begins. If fertilization does not occur, the egg is expelled from the uterus during menstruation, which occurs when the lining of the uterus is shed. Sometimes fertilization occurs outside the uterus, often when the egg is still in the fallopian tube; this is called an ectopic pregnancy and can be dangerous if not treated.

Ovarian cancer is the fifth leading cause of cancer-related death in women. It is estimated to be responsible for the deaths of 13,980 women this year, making it the deadliest of all female reproductive system cancer types.

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New Research Using Lifeline® Fallopian Tube Epithelial Cells

High-grade serous ovarian cancer (HGSOC) has a poor prognosis, largely due to a lack of early detection markers and few treatment options for treatment-resistant cases. To develop new biomarkers for early detection of HGSOC, Wang et al. (opens in new window) investigated the role of protein tyrosine phosphatase PTPL1 in HGSOC. Using paired tumor and adjacent normal tissue samples from a cohort of 97 patients with HGSOC, the researchers found that mRNA and protein levels of PTPL1 were decreased in patient tumor tissue compared with adjacent normal tissue; 36/97 patients were classified as having low PTPL1 expression and 61/97 as having high PTPL1 expression. When analyzed in more detail, the authors found that reduced PTPL1 levels were a poor prognostic factor in HGSOC: lower PTPL1 levels were correlated with more advanced clinical stage and shorter mean survival. Advanced clinical stage was also correlated with poor overall survival. In particular, tumor stage and PTPL1 expression were identified as independent prognostic factors in this patient cohort.

To define the potential mechanism by which PTPL1 acts in HGSOC, the group evaluated PTPL1 expression in primary serous ovarian cancer cells (POC cells) and the OV-90 ovarian cancer cell line. Compared with Lifeline® normal human fallopian tube epithelial cells, the authors found that PTPL1 expression was lower in POC and OV-90 cells, consistent with their results in patient tissue samples. Using OC-90 cells, the researchers next investigated the role of PTPL1 on cancer cell behavior. PTPL1 overexpression inhibited cell proliferation and invasion, whereas PTPL1 knockdown increased these tumor-promoting properties.

The group next determined the role of PTPL1 on regulation of the NF-kB inhibitor, IkBa. Levels of IkBa phosphorylation on tyrosine 42 (IkBa-p-Y42) in tumor tissue samples from patients with HGSOC were negatively correlated with PTP1 expression, suggesting that PTPL1 may regulate IkBa phosphorylation. Consistent with this, IkBa-p-Y42 was reduced or increased in cells overexpressing PTPL1 or with PTPL1 knockdown, respectively. Interestingly, inhibition of IkBa with BAY 11-0785 or overexpression of the phospho-mutant IkBa-Y42A reduced OV-90 cancer cell proliferation and invasion.

Together, the results of this study suggest that PTPL1 is a potential tumor suppressor that regulates inhibition of NF-kB signaling to attenuate cell proliferation and invasion.

Join us here on the blog every other week to learn more about our cell systems and how research groups around the world are using them. Let us know how you are using Lifeline® products and your work could be featured here too!

Ovarian cancer statistics from www.cancer.org (opens in new window).

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