Podoplanin: An emerging cancer biomarker and therapeutic target

Our plain-English summary of Podoplanin: An emerging cancer biomarker and therapeutic target, by H. Krishnan, J. Rayes, T. Miyashita, et al (Cancer Science, 2018).

The study

• Authors: H. Krishnan, J. Rayes, T. Miyashita, G. Ishii, E.P. Retzbach, S.A. Sheehan, A. Takemoto, Y.W. Chang, K. Yoneda, J. Asai, L. Jensen, L. Chalise, A. Natsume, G.S. Goldberg
• Journal: Cancer Science
• Published: 2018;109(5):1292-1299
• Type of article: Review
• Cited by: 163 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.

© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

In plain English

This article was a review, not a new study. The authors described published research on podoplanin, a protein found on some cancer cells, on cancer associated fibroblasts and on inflammatory macrophages. They asked how it might serve as a cancer marker and as a treatment target. The article did not study asbestos or any fiber exposure. In the work reviewed, antibodies against podoplanin decreased tumor load in animal models of glioma, mesothelioma and lung cancer. Chips coated with podoplanin antibodies captured and detected malignant pleural mesothelioma cells in preclinical models. In one cited melanoma study, podoplanin was found in tumor cells from 38 of 55 patients. In that study, only 4 of 30 patients without podoplanin on their tumor fibroblasts had sentinel lymph node metastasis. In a cited glioma study, tumors grew markedly slower in about 60% of mice treated with podoplanin-targeting CAR-T cells. The authors concluded that podoplanin has clear potential as a cancer biomarker and therapeutic target. They noted a concern that such CAR-T cells might also attack normal cells that carry podoplanin.

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: Review article summarizing published laboratory, animal and patient studies on podoplanin (PDPN) in cancer
• Who was studied: No study population of its own. The authors reviewed published studies of podoplanin in several cancers, including glioma, squamous cell carcinoma, mesothelioma and melanoma, mostly in cell cultures and animal models.
• Exposure: No asbestos or other fiber exposure was studied. The article concerns the protein podoplanin and agents that target it (antibodies, CAR-T cells, lectins and synthetic compounds).
• Main results:
  • Reviewed finding: antibodies that bind podoplanin (NZ-1, its derivatives such as NZ-8 and NZ-12, and MS-1) decreased tumor load in xenograft (animal) models of glioma, mesothelioma and lung cancer.
  • Reviewed finding: circulating tumor cell chips coated with podoplanin antibodies, still in development, were used to capture and detect malignant pleural mesothelioma cells in preclinical models.
  • Reviewed finding (one cited melanoma study): podoplanin was found in tumor cells from 38 of 55 melanoma patients (69.1%). Only 4 of 30 (13.3%) patients without podoplanin on cancer associated fibroblasts had sentinel lymph node metastasis. Patients with podoplanin-positive fibroblasts had lower disease-free survival (P = .0148).
  • Reviewed finding: podoplanin in precancerous oral lesions (such as oral leukoplakias) correlated with a 3-fold increase in their transformation into cancer, compared with lesions without podoplanin.
  • Reviewed finding (glioma mouse model): in approximately 60% of mice treated with NZ-1-CAR-T cells, tumors grew markedly slower and the mice survived significantly longer than control groups.
• The authors' conclusion: The authors concluded that podoplanin is expressed by many types of tumor cells and that high podoplanin expression is associated with reduced survival and cancer aggression. In their view, podoplanin has clear potential as a cancer biomarker and therapeutic target.
• Limitations the authors state:
  • The authors noted a concern that podoplanin-targeting CAR-T therapy could destroy normal cells that also express podoplanin, including lymphatic endothelium and type I lung alveolar cells.

Topics

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Biomarker, Glycoprotein, Fibroblast, Macrophage, Metastasis, Inflammation, CAR-T Cell.

Related studies

• Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity — M.K. Kaneko, S. Yamada, et al. (2017)
• Therapeutic efficacy evaluation of radioimmunotherapy with 90 Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma — H. Sudo, A.B. Tsuji, et al. (2019)
• Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation — S. Takeuchi, K. Fukuda, et al. (2017)
• Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model — S. Abe, M.K. Kaneko, et al. (2016)
• Establishment of Mouse Monoclonal Antibody LpMab-13 Against Human Podoplanin — S. Ogasawara, M.K. Kaneko, et al. (2016)
• Podoplanin overexpression in human mesothelioma cell lines enhances the tumorigenic phenotype — E. Yamaki, T. Yajima, et al. (2013)

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