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Vasohibin-1 and -2 in pulmonary lymphangioleiomyomatosis (LAM) cells associated with angiogenic and prognostic factors.

Abstract
Lymphangioleiomyomatosis (LAM) is a rare pulmonary neoplasm, clinically associated with dyspnea and respiratory failure. Current therapeutic modalities do not necessarily reach satisfactory outcome and novel therapeutic approaches are currently warranted. Therefore, in this study, we focused on vasohibin-1 (VASH1) and -2 (VASH2); VASH1 terminated and VASH2 promoted angiogenesis. In addition, both VASH1/2 were reported to influence the progression of various human malignancies. We first performed hierarchical clustering analysis to attempt to classify 36 LAM cases into three different clusters according to immunoreactivity of VASH1/2 and other angiogenic and prognostic factors of LAM; VEGFR1/2/3, p-mTOR, p-S6, p-4EBP, ERĪ±, PgR, MMP2, and MMP9. The cluster harboring higher angiogenic factors had higher VASH1/2 status. VASH1 was significantly positively correlated with VEGFR2, MMP9, and p-mTOR (p-value <0.05), and VASH2 with both angiogenic and prognostic factors including VEGFR1, PgR, MMP9, p-mTOR, p-S6, and p-4EBP (p-value <0.05). Subsequent PCR array of angiogenic genes demonstrated that high VASH1 mRNA was significantly positively associated with the status of SPHK1 and TYPM, lower EGF and EFNB2 (p-value <0.05), and high VASH2 mRNA negatively with MMP2 (p-value <0.05). VASH1 was considered to be up-regulated by activation of angiogenesis, whereas VASH2 could influence the angiogenesis and progression of LAM.
AuthorsChihiro Inoue, Yasuhiro Miki, Ryoko Saito-Koyama, Kazuma Kobayashi, Kuniaki Seyama, Yoshinori Okada, Hironobu Sasano
JournalPathology, research and practice (Pathol Res Pract) Vol. 230 Pg. 153758 (Feb 2022) ISSN: 1618-0631 [Electronic] Germany
PMID35026646 (Publication Type: Journal Article)
CopyrightCopyright © 2022 Elsevier GmbH. All rights reserved.
Chemical References
  • Angiogenic Proteins
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • VASH1 protein, human
  • VASH2 protein, human
Topics
  • Adult
  • Angiogenic Proteins (genetics, metabolism)
  • Biomarkers, Tumor (genetics, metabolism)
  • Cell Cycle Proteins (genetics, metabolism)
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms (genetics, metabolism, pathology)
  • Lymphangioleiomyomatosis (genetics, metabolism, pathology)
  • Male
  • Middle Aged
  • Neovascularization, Pathologic
  • Young Adult

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