Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients
Background: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and...
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2944 |
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| author | Leticia Oliveira-Ferrer Barbara Schmalfeldt Johannes Dietl Catharina Bartmann Udo Schumacher Christine Stürken |
| author_facet | Leticia Oliveira-Ferrer Barbara Schmalfeldt Johannes Dietl Catharina Bartmann Udo Schumacher Christine Stürken |
| author_sort | Leticia Oliveira-Ferrer |
| collection | DOAJ |
| description | Background: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and metastasis. Methods: In the present study, HA deposition in tissue sections was analyzed by hyaluronan-binding protein (HABP) ligand histochemistry in 17 borderline tumors and 102 primary and 20 recurrent ovarian cancer samples. The intensity and, particularly, localization of the HA deposition were recorded: for the localization, the pericellular deposition around the ovarian cancer cells was distinguished from the deposition within the stromal compartment. These histochemical data were correlated with clinical and pathological parameters. Additionally, within a reduced subgroup of ovarian cancer samples (<i>n</i> = 70), the RNA levels of several HA-associated genes were correlated with the HA localization and intensity. Results: Both stroma-localized and pericellular tumor-cell-associated HA deposition were observed. Cancer-cell pericellular HA deposition, irrespective of its staining intensity, was significantly associated with malignancy, and in the primary ovarian cancer cohort, it represents an independent unfavorable prognostic marker for overall survival. Furthermore, a significant association between high CD44, HAS2 and HAS3 mRNA levels and a cancer-cell pericellular HA-deposition pattern was noted. In contrast, stromal hyaluronan deposition had no impact on ovarian cancer prognosis. Conclusions: In conclusion, the site of HA deposition is of prognostic value, but the amount deposited is not. The significant association of only peritumoral cancer-cell HA deposition with high CD44 mRNA expression levels suggests a pivotal role of the CD44–HA signaling axis for malignant progression in ovarian cancer. |
| first_indexed | 2024-03-09T18:27:48Z |
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| id | doaj.art-d79d59cb4d5543f78e27ae938c8ff5ca |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:48Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d79d59cb4d5543f78e27ae938c8ff5ca2023-11-24T07:46:36ZengMDPI AGBiomedicines2227-90592022-11-011011294410.3390/biomedicines10112944Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer PatientsLeticia Oliveira-Ferrer0Barbara Schmalfeldt1Johannes Dietl2Catharina Bartmann3Udo Schumacher4Christine Stürken5Department of Gynaecology and Gynaecologic Oncology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Gynaecology and Gynaecologic Oncology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Obstetrics and Gynaecology, University of Wuerzburg, 97080 Wuerzburg, GermanyDepartment of Obstetrics and Gynaecology, University of Wuerzburg, 97080 Wuerzburg, GermanyDepartment of Anatomy and Experimental Morphology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Anatomy and Experimental Morphology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, GermanyBackground: Hyaluronan (HA), a component of the extracellular matrix, is frequently increased under pathological conditions including cancer. Not only stroma cells but also cancer cells themselves synthesize HA, and the interaction of HA with its cognate receptors promotes malignant progression and metastasis. Methods: In the present study, HA deposition in tissue sections was analyzed by hyaluronan-binding protein (HABP) ligand histochemistry in 17 borderline tumors and 102 primary and 20 recurrent ovarian cancer samples. The intensity and, particularly, localization of the HA deposition were recorded: for the localization, the pericellular deposition around the ovarian cancer cells was distinguished from the deposition within the stromal compartment. These histochemical data were correlated with clinical and pathological parameters. Additionally, within a reduced subgroup of ovarian cancer samples (<i>n</i> = 70), the RNA levels of several HA-associated genes were correlated with the HA localization and intensity. Results: Both stroma-localized and pericellular tumor-cell-associated HA deposition were observed. Cancer-cell pericellular HA deposition, irrespective of its staining intensity, was significantly associated with malignancy, and in the primary ovarian cancer cohort, it represents an independent unfavorable prognostic marker for overall survival. Furthermore, a significant association between high CD44, HAS2 and HAS3 mRNA levels and a cancer-cell pericellular HA-deposition pattern was noted. In contrast, stromal hyaluronan deposition had no impact on ovarian cancer prognosis. Conclusions: In conclusion, the site of HA deposition is of prognostic value, but the amount deposited is not. The significant association of only peritumoral cancer-cell HA deposition with high CD44 mRNA expression levels suggests a pivotal role of the CD44–HA signaling axis for malignant progression in ovarian cancer.https://www.mdpi.com/2227-9059/10/11/2944ovarian cancerstromal hyaluronantumor-associated hyaluronan staining patternhyaluronan-related enzymes |
| spellingShingle | Leticia Oliveira-Ferrer Barbara Schmalfeldt Johannes Dietl Catharina Bartmann Udo Schumacher Christine Stürken Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients Biomedicines ovarian cancer stromal hyaluronan tumor-associated hyaluronan staining pattern hyaluronan-related enzymes |
| title | Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients |
| title_full | Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients |
| title_fullStr | Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients |
| title_full_unstemmed | Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients |
| title_short | Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients |
| title_sort | ovarian cancer cell pericellular hyaluronan deposition negatively impacts prognosis of ovarian cancer patients |
| topic | ovarian cancer stromal hyaluronan tumor-associated hyaluronan staining pattern hyaluronan-related enzymes |
| url | https://www.mdpi.com/2227-9059/10/11/2944 |
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