Usage Information
Citation Information: J Clin Invest. 2021;131(10):e144225. https://doi.org/10.1172/JCI144225.
Abstract
Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects.
Authors
Zhen Lu, Angelica Ortiz, Ioannis I. Verginadis, Amy R. Peck, Farima Zahedi, Christina Cho, Pengfei Yu, Rachel M. DeRita, Hongru Zhang, Ryan Kubanoff, Yunguang Sun, Andrew T. Yaspan, Elise Krespan, Daniel P. Beiting, Enrico Radaelli, Sandra W. Ryeom, J. Alan Diehl, Hallgeir Rui, Constantinos Koumenis, Serge Y. Fuchs
Usage data is cumulative from July 2024 through July 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 680 | 130 |
| 103 | 102 | |
| Figure | 457 | 1 |
| Supplemental data | 67 | 18 |
| Citation downloads | 79 | 0 |
| Totals | 1,386 | 251 |
| Total Views | 1,637 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)