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Volume 12
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Article

Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility

by
Iwona Bednarz-Misa
1,
Dorota Diakowska
2,3,
Izabela Szczuka
1,
Paulina Fortuna
1,
Agnieszka Kubiak
1,
Joanna Rosińczuk
3 and
Małgorzata Krzystek-Korpacka
1,*
1
Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland
2
Department of Gastrointestinal and General Surgery, Wroclaw Medical University, 50-368 Wroclaw, Poland
3
Department of Nervous System Diseases, Wroclaw Medical University, 51-618 Wroclaw, Poland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1463; https://doi.org/10.3390/cancers12061463
Submission received: 9 April 2020 / Revised: 30 May 2020 / Accepted: 1 June 2020 / Published: 4 June 2020
(This article belongs to the Special Issue Interleukin in Cancer Pathogenesis and Treatment)
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Abstract

Immunosuppressive interleukins (IL)-4 and 13 may directly promote cancer but neither their status nor role in gastrointestinal tract is clarified. We aim at quantifying ILs and their receptors in paired normal-tumor samples (n = 49/51) and sera (n = 263), using immunoassays and RTqPCR, and screening for their effect on colonic cancer cells. Both ILs were elevated locally at protein level in all cancers but only IL13 transcripts in colon were upregulated. Interleukin and their receptor expression reflected cancer pathology to varying degrees, with the association frequently inverse and manifested in non-cancerous tissue. Positive correlation with cancer-promoting genes BCL2, BCLxL, HIF1A, VEGFA, ACTA2, CCL2, PTGS2, and CDKN1A, but not Ki67, was demonstrated, particularly for ILs’ receptors. Circulating IL-4 was elevated in all, while IL-13 only in colorectal or esophageal cancers, reflecting their advancement. IL4Ra and IL13Ra1 transcripts were downregulated by hypoxia and, in Caco-2, also by IL-4. Interleukin stimulation slightly improved colonic cancer cell viability, weakly upregulating BCL2 and Ki67 in HCT116 and HT-29. It affected cell motility more markedly and was consistently accompanied by upregulation of claudin-2. Gastrointestinal tract cancers are associated with IL-4 and IL-13 upregulation, which may facilitate cancer growth. Targeting both interleukins as an antineoplastic strategy warrants further investigation.
Keywords: colorectal cancer; esophageal squamous cell carcinoma; gastric adenocarcinoma; immunotherapy; molecular margin; interleukin colorectal cancer; esophageal squamous cell carcinoma; gastric adenocarcinoma; immunotherapy; molecular margin; interleukin

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MDPI and ACS Style

Bednarz-Misa, I.; Diakowska, D.; Szczuka, I.; Fortuna, P.; Kubiak, A.; Rosińczuk, J.; Krzystek-Korpacka, M. Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility. Cancers 2020, 12, 1463. https://doi.org/10.3390/cancers12061463

AMA Style

Bednarz-Misa I, Diakowska D, Szczuka I, Fortuna P, Kubiak A, Rosińczuk J, Krzystek-Korpacka M. Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility. Cancers. 2020; 12(6):1463. https://doi.org/10.3390/cancers12061463

Chicago/Turabian Style

Bednarz-Misa, Iwona, Dorota Diakowska, Izabela Szczuka, Paulina Fortuna, Agnieszka Kubiak, Joanna Rosińczuk, and Małgorzata Krzystek-Korpacka. 2020. "Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility" Cancers 12, no. 6: 1463. https://doi.org/10.3390/cancers12061463

APA Style

Bednarz-Misa, I., Diakowska, D., Szczuka, I., Fortuna, P., Kubiak, A., Rosińczuk, J., & Krzystek-Korpacka, M. (2020). Interleukins 4 and 13 and Their Receptors Are Differently Expressed in Gastrointestinal Tract Cancers, Depending on the Anatomical Site and Disease Advancement, and Improve Colon Cancer Cell Viability and Motility. Cancers, 12(6), 1463. https://doi.org/10.3390/cancers12061463

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