Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
25
03
2021
revised:
23
06
2021
accepted:
20
07
2021
pubmed:
28
7
2021
medline:
23
3
2022
entrez:
27
7
2021
Statut:
ppublish
Résumé
Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood. By integrating complementary gene and protein LAM signatures, and single-cell and bulk tissue transcriptome profiles, we show sources of disease heterogeneity, and how they correspond to cancer molecular portraits. Subsets of LAM diseased cells differ with respect to gene expression profiles related to hormones, metabolism, proliferation, and stemness. Phenotypic diseased cell differences are identified by evaluating lumican (LUM) proteoglycan and YB1 transcription factor expression in LAM lung lesions. The RUNX1 and IRF1 transcription factors are predicted to regulate LAM cell signatures, and both regulators are expressed in LAM lung lesions, with differences between spindle-like and epithelioid LAM cells. The cancer single-cell transcriptome profiles most similar to those of LAM cells include a breast cancer mesenchymal cell model and lines derived from pleural mesotheliomas. Heterogeneity is also found in LAM lung tissue, where it is mainly determined by immune system factors. Variable expression of the multifunctional innate immunity protein LCN2 is linked to disease heterogeneity. This protein is found to be more abundant in blood plasma from LAM patients than from healthy women. IMPLICATIONS: This study identifies LAM molecular and cellular features, master regulators, cancer similarities, and potential causes of disease heterogeneity.
Identifiants
pubmed: 34312290
pii: 1541-7786.MCR-21-0220
doi: 10.1158/1541-7786.MCR-21-0220
pmc: PMC8568632
mid: NIHMS1729426
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1840-1853Subventions
Organisme : Intramural NIH HHS
ID : ZIA HL002541
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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