Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform

Our plain-English summary of Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform, by H. Chen, N. Haddadi, X. Zhu, et al (Journal of Oncology, 2022).

The study

• Authors: H. Chen, N. Haddadi, X. Zhu, D. Hatoum, S. Chen, N.T. Nassif, Y. Lin, E.M. McGowan
• Journal: Journal of Oncology
• Published: 2022;2022:2250407
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance.

Objective: The objective is to examine the expression profile of the SphK1a and SPhK1b isoforms in human cancer and noncancer tissues and cell lines and explore their clinical relevance.

Methods: We used PCR to qualitatively examine the expression profile of these two isoforms in breast, liver, and prostate cancer tissues plus paired adjacent tissues and in 11 cancer and normal cell lines (breast, cervical, bone, prostate, colon, brain, mesothelioma tumor and benign, and human kidney cells).

Results: We found that SphK1a was ubiquitously expressed in all cancer cells and tissues tested; in contrast, SphK1b was only expressed in selective cell types in breast, prostate, and lung cancer.

Conclusions: Our data suggest that SphK1a is important for generic SphK1/S1P functions, and SphK1b mediates specialized and/or unique pathways in a specific type of tissue and could be a biomarker for cancer. This discovery is important for future SphK1-related cancer research and may have clinical implications in drug development associated with SphK1-directed cancer treatment.

Copyright © 2022 Hongjie Chen et al.

In plain English

This laboratory study tested whether two forms of the enzyme sphingosine kinase 1, called SphK1a and SphK1b, are present in human cancer cells and tissues. It did not study asbestos exposure. Using a non-quantitative RT-PCR test, the authors examined 24 cell lines, including mesothelioma lines. They also examined tumor plus adjacent tissue from 6 liver cancer, 7 prostate cancer and 15 breast cancer patients in Guangzhou, China. SphK1a was detected in all 24 cell lines. SphK1b was detected in 5 of 6 epithelioid mesothelioma lines, 2 of 3 benign mesothelioma lines and none of 3 biphasic mesothelioma lines. In tissues, SphK1b was found in no liver samples, 5 of 7 prostate tumors and 9 of 15 breast tumors, with no clear difference between tumor and adjacent tissue. The authors concluded that SphK1a appears ubiquitous while SphK1b is selective by cell and tissue type and may be a biomarker for some cancers. They stated that the significance of the mesothelioma findings has not yet been defined. They noted the test was qualitative and the patient sample was small.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study using a qualitative (non-quantitative) RT-PCR test on human cell lines and on surgical tumor tissue with matched adjacent tissue
• Who was studied: 24 human cell lines: breast, cervical, bone, prostate, colon, brain, epithelioid, biphasic and benign mesothelioma, and human embryonic kidney. Tissue from 6 patients with hepatocellular carcinoma (liver cancer), 7 with prostate cancer and 15 with breast cancer, with matching adjacent tissue, from hospitals of Sun Yat-sen University, Guangzhou, China. The mesothelioma cell lines were donated by researchers including the Asbestos Disease Research Institute, Sydney. Collection dates are not given.
• Exposure: No asbestos or other exposure was studied. The study measured whether the SphK1a and SphK1b gene forms were detectable.
• Main results:
  • SphK1a was detected in all 24 cell lines tested (Table 1: 24/24).
  • Mesothelioma cell lines: SphK1b was detected in 5 of 6 epithelioid lines and 2 of 3 benign mesothelioma lines.
  • Mesothelioma cell lines: SphK1b was not detected in any of the 3 biphasic lines.
  • Other cell lines: SphK1b was detected in 1 of 2 breast cancer lines (MCF-7) and in none of the prostate cancer lines.
  • Liver tissue: SphK1b was not detected in any of the 6 liver cancer samples or their adjacent tissues.
  • Prostate tissue: SphK1b was detected in 71% (5/7) of prostate cancer tissues and 57% (4/7) of adjacent tissues.
  • Breast tissue: SphK1b was detected in 60% (9/15) of breast cancer samples and 53% (8/15) of adjacent samples. SphK1a was detected in 93% (14/15) of breast cancer samples.
  • Breast tissue: all 6 Grade 3 breast cancers were positive for SphK1b, compared with 2 of 8 Grade 1 and 2 cancers. ER-positive cancers were more often positive for SphK1b (6/8) than ER-negative cancers (3/7).
  • No clear difference in isoform expression was found between cancer tissue and adjacent tissue.
  • Computer modelling predicted that SphK1b RNA is less stable than SphK1a RNA.
• The authors' conclusion: The authors concluded that SphK1a expression appears ubiquitous while SphK1b expression is selective by cell and tissue type, and that SphK1b may function as a biomarker for some cancer types. They stated that the significance of the mesothelioma cell line findings has not yet been defined.
• Limitations the authors state:
  • The test was qualitative PCR, not quantitative PCR.
  • The number of patients was relatively small, which limits how far the findings can be generalized.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Mesothelioma, Lung Cancer, Biomarker, Discovery.

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