MAY 30, 2020 6:57 AM PDT

Linking an Aggressive Tumor Factor to the Innate Immune Response

WRITTEN BY: Jasper Cantrell

Epithelial Ovarian Cancer (EOC) is a cancer of the fallopian tubes with a low five-year survival rate and a tendency to develop chemoresistance. The current first-line treatment is platinum chemotherapy. Several other possible treatments, such as poly ADP ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors, are in development but not available for actual use. There remains a need for further treatment options, however. The small secreted human epididymis protein 4 (HE4) is a biomarker of EOC, with several papers noting its overexpression in aggressive cancer phenotypes. A team from Rhode Island decided to investigate HE4’s possible effect on the tumor microenvironment, rather than its intracellular role.

HE4 has previously been shown to promote tumorigenesis, metastasis, and chemoresistance in EOC tissue. While many factors with pro-tumor activities act on intra-cellular pathways, some can also influence the microenvironment around a tumor. The team began by examining the mRNA levels of peripheral blood mononuclear cells (PBMCs) after the addition of recombinant HE4. They found many proteins were upregulated, but of interest to them was interleukin 8 (IL8) and hypoxia inducible factor alpha (H1F1A). Both are important pro-tumor signaling factors and have come up in previous work. They are also both downstream factors of the STAT3 signaling pathway. The abnormal activation of the STAT3 pathway is common in many cancers, including EOC.

They proceeded by examining the levels of IL8 and H1F1A in HE4 treated cells with and without a STAT3 inhibitor to determine the connection between the three. HE4 treatment caused IL8 and H1F1A levels to increase substantially, alongside an increase in activated STAT3. With both HE4 and the STAT3 inhibitor, they saw a suppression of the stimulated levels seen with HE4 alone. Levels of IL8 and H1F1A remained high, however. An in vitro test found that HE4 was capable of promoting angiogenesis as well. This stimulation was mildly suppressed with the addition of the STAT3 inhibitor. Finally, a quick examination of HE4 and IL8 levels in EOC tissue compared to healthy ovarian tissue showed a strong positive correlation between HE4 and IL8 levels. Both were upregulated in EOC, and CD8+ cytotoxic T cells had a strong negative correlation with both of their levels. CD8+ T cells are part of the immune system, usually responsible for getting rid of cancer cells.

The team concludes, “These findings indicate that HE4 could have an important role in regulating both angiogenesis and suppression of immune cell infiltrate and responses.” HE4’s upregulation was already a key biomarker in EOC. Linking HE4 to the STAT3 pathway, a signaling pathway known to be abnormally active in many cancers, and IL8, a protein involved in the regulation of the immune system response, furthers our understanding of the protein and its role. Already a biomarker, it could lead to a new target in EOC treatment.

Sources: Nature, Osmosis

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
JUL 08, 2021
Cancer
Activating p53 May Boost Efficacy of Cancer Immunotherapy
JUL 08, 2021
Activating p53 May Boost Efficacy of Cancer Immunotherapy
Pharmacological activation of the p53 protein in cancer cells leads to an anti-tumor immune response in lab tests. These ...
SEP 02, 2021
Cancer
When Cholesterol Doesn't Kill Cancer, it Makes it Stronger!
SEP 02, 2021
When Cholesterol Doesn't Kill Cancer, it Makes it Stronger!
High cholesterol is associated with an increased risk of several types of cancer, and cancer patients with high choleste ...
SEP 18, 2021
Genetics & Genomics
Cancer Genes Might Aim for the Immune System, Not Growth Promotion
SEP 18, 2021
Cancer Genes Might Aim for the Immune System, Not Growth Promotion
The DNA in our cells can accumulate damage over may years. Environmental influences like UV light or cigarette smoke may ...
OCT 14, 2021
Clinical & Molecular DX
Weighing Cancer Cells Helps Predict Treatment Outcomes
OCT 14, 2021
Weighing Cancer Cells Helps Predict Treatment Outcomes
Not all cancer patients respond to oncology treatments in the same way. Some might show signs of improvement as the ther ...
OCT 25, 2021
Cell & Molecular Biology
The Labroots 2021 Cell Biology Virtual Event Poster Winner: 5-Azacytidine Treatment & Lung Cancer
OCT 25, 2021
The Labroots 2021 Cell Biology Virtual Event Poster Winner: 5-Azacytidine Treatment & Lung Cancer
Labroots virtual events are a great place to share research and learn about others work. These events feature participan ...
NOV 23, 2021
Clinical & Molecular DX
Scientists Enter Uncharted Territory of the Cancer Genome, Emerge Victorious
NOV 23, 2021
Scientists Enter Uncharted Territory of the Cancer Genome, Emerge Victorious
Cancer is a genetic disease—it stems from specific changes in the DNA sequences of the cancer cell genome. Over th ...
Loading Comments...