Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings
Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of <i>ACKR2</i> and <i>ACKR4</i> exp...
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MDPI AG
2020-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/1/8 |
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| author | Paulina Lewandowska Jaroslaw Wierzbicki Marek Zawadzki Anil Agrawal Małgorzata Krzystek-Korpacka |
| author_facet | Paulina Lewandowska Jaroslaw Wierzbicki Marek Zawadzki Anil Agrawal Małgorzata Krzystek-Korpacka |
| author_sort | Paulina Lewandowska |
| collection | DOAJ |
| description | Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of <i>ACKR2</i> and <i>ACKR4</i> expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, <i>ACKR2</i> was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, <i>ACKR4</i> was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in <i>ACKR4</i> expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, <i>ACKR4</i> downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. <i>ACKR4</i> expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration. |
| first_indexed | 2024-03-10T13:49:32Z |
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| id | doaj.art-8823f4c951ab41e48d42b1d6022f6dc3 |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:49:32Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8823f4c951ab41e48d42b1d6022f6dc32023-11-21T02:16:47ZengMDPI AGBiomolecules2218-273X2020-12-01111810.3390/biom11010008Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological FindingsPaulina Lewandowska0Jaroslaw Wierzbicki1Marek Zawadzki2Anil Agrawal3Małgorzata Krzystek-Korpacka4Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandDepartment of Minimally Invasive Surgery and Proctology, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Oncological Surgery, Regional Specialist Hospital, 51-124 Wroclaw, PolandThe 2nd Department of General and Oncological Surgery, Wroclaw Medical University, 50-556 Wroclaw, PolandDepartment of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, PolandFacilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of <i>ACKR2</i> and <i>ACKR4</i> expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, <i>ACKR2</i> was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, <i>ACKR4</i> was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in <i>ACKR4</i> expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, <i>ACKR4</i> downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. <i>ACKR4</i> expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.https://www.mdpi.com/2218-273X/11/1/8resolution of inflammationchemopreventiondecoy receptorscolorectal adenomascolorectal cancerCC chemokines |
| spellingShingle | Paulina Lewandowska Jaroslaw Wierzbicki Marek Zawadzki Anil Agrawal Małgorzata Krzystek-Korpacka Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings Biomolecules resolution of inflammation chemoprevention decoy receptors colorectal adenomas colorectal cancer CC chemokines |
| title | Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings |
| title_full | Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings |
| title_fullStr | Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings |
| title_full_unstemmed | Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings |
| title_short | Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings |
| title_sort | biphasic expression of atypical chemokine receptor ackr 2 and ackr4 in colorectal neoplasms in association with histopathological findings |
| topic | resolution of inflammation chemoprevention decoy receptors colorectal adenomas colorectal cancer CC chemokines |
| url | https://www.mdpi.com/2218-273X/11/1/8 |
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