Sprouting Angiogenesis in Human Pituitary Adenomas
IntroductionAngiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.Materials and Methods219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes w...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.875219/full |
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| author | Jie Zhou Yaomin Hu Wende Zhu Chuansheng Nie Wenxiu Zhao Alexander T. Faje Kay E. Labelle Brooke Swearingen Hang Lee E. Tessa Hedley-Whyte Xun Zhang Pamela S. Jones Karen K. Miller Anne Klibanski Yunli Zhou Roy J. Soberman |
| author_facet | Jie Zhou Yaomin Hu Wende Zhu Chuansheng Nie Wenxiu Zhao Alexander T. Faje Kay E. Labelle Brooke Swearingen Hang Lee E. Tessa Hedley-Whyte Xun Zhang Pamela S. Jones Karen K. Miller Anne Klibanski Yunli Zhou Roy J. Soberman |
| author_sort | Jie Zhou |
| collection | DOAJ |
| description | IntroductionAngiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.Materials and Methods219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice.Results71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFβ). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice.ConclusionHuman pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors. |
| first_indexed | 2024-12-12T13:48:31Z |
| format | Article |
| id | doaj.art-47bb963aef744161bbbf0c8bfbe4471c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T13:48:31Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-47bb963aef744161bbbf0c8bfbe4471c2022-12-22T00:22:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.875219875219Sprouting Angiogenesis in Human Pituitary AdenomasJie Zhou0Yaomin Hu1Wende Zhu2Chuansheng Nie3Wenxiu Zhao4Alexander T. Faje5Kay E. Labelle6Brooke Swearingen7Hang Lee8E. Tessa Hedley-Whyte9Xun Zhang10Pamela S. Jones11Karen K. Miller12Anne Klibanski13Yunli Zhou14Roy J. Soberman15Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeurosurgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesBiostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesDepartment of Pathology (Neuropathology), Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeurosurgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNeuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesNephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesIntroductionAngiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors.Materials and Methods219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice.Results71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFβ). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice.ConclusionHuman pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.https://www.frontiersin.org/articles/10.3389/fonc.2022.875219/fullsprouting angiogenesisangiogenic gene expressionangiogenesis inhibitionendothelial markerRb1 miceVEGF inhibitor |
| spellingShingle | Jie Zhou Yaomin Hu Wende Zhu Chuansheng Nie Wenxiu Zhao Alexander T. Faje Kay E. Labelle Brooke Swearingen Hang Lee E. Tessa Hedley-Whyte Xun Zhang Pamela S. Jones Karen K. Miller Anne Klibanski Yunli Zhou Roy J. Soberman Sprouting Angiogenesis in Human Pituitary Adenomas Frontiers in Oncology sprouting angiogenesis angiogenic gene expression angiogenesis inhibition endothelial marker Rb1 mice VEGF inhibitor |
| title | Sprouting Angiogenesis in Human Pituitary Adenomas |
| title_full | Sprouting Angiogenesis in Human Pituitary Adenomas |
| title_fullStr | Sprouting Angiogenesis in Human Pituitary Adenomas |
| title_full_unstemmed | Sprouting Angiogenesis in Human Pituitary Adenomas |
| title_short | Sprouting Angiogenesis in Human Pituitary Adenomas |
| title_sort | sprouting angiogenesis in human pituitary adenomas |
| topic | sprouting angiogenesis angiogenic gene expression angiogenesis inhibition endothelial marker Rb1 mice VEGF inhibitor |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.875219/full |
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