ArticleThe Journal of clinical investigation2016
Matricellular protein SPARCL1 regulates tumor microenvironment-dependent endothelial cell heterogeneity in colorectal carcinoma.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Integrated analysis reveals down-regulation of SPARCL1 is correlated with cervical cancer development and progression.Cancer biomarkers : section A of Disease markers · 2018Pooled it
- IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin-directed vascular barrier disruption.The Journal of clinical investigation · 2019Trial
- Lipid Accumulation Promotes Tumorigenic Behaviour of Colorectal Cancer Cells.Journal of cellular and molecular medicine · 2026Article
- Teneurins Are SPARCL1 Receptors.bioRxiv : the preprint server for biology · 2026Article
- Article
- Proteomic pathways mediating low socioeconomic status and cardiovascular events in older adults in CHS and ARIC.Atherosclerosis · 2026Article
- Sparcl1 mitigates abdominal aortic aneurysm through inhibiting lymphangiogenesis-mediated TLS formation.Nature immunology · 2026Article
- Immunoregulatory Roles of Tumor-Originated Pericytes Identified by Single-Cell Analysis in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrin β6 expression in colorectal cancer cells promotes liver metastasis through enhanced adhesion to endothelial fibronectin.International journal of cancer · 2025Article
- Prognostic Significance ofBiology · 2025Article
- Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.Cell death and differentiation · 2025Article
- Identification of Potential Therapeutic Targets for Coronary Atherosclerosis from an Inflammatory Perspective Through Integrated Proteomics and Single-Cell Omics.International journal of molecular sciences · 2025Article
- Article
- The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1.Stem cell reports · 2025Article
- AMIGO2 characterizes cancer-associated fibroblasts in metastatic colon cancer and induces the release of paracrine active tumorigenic secretomes.The Journal of pathology · 2025Article
- Elevated Serum Extracellular Vesicle-Packaged SPARC in Hypertension: A Cross-Sectional Study in a Middle-Aged and Elderly Population.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Skin immune-mesenchymal interplay within tertiary lymphoid structures promotes autoimmune pathogenesis in hidradenitis suppurativa.Immunity · 2024Article
- Revolutionizing prognostic predictions in colorectal cancer: Macrophage‑driven transcriptional insights from single‑cell RNA sequencing and gene co‑expression network analysis.Oncology letters · 2024Article
- The oncogenic functions of SPARCL1 in bladder cancer.Journal of cellular and molecular medicine · 2024Article
- Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.Nature communications · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
Abstract
Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.