Usage Information
Abstract
Small primary breast cancers can show surprisingly high potential for metastasis. Clinical decision-making for tumor aggressiveness, including molecular profiling, relies primarily on analysis of the cancer cells. Here we show that this analysis is insufficient — that the stromal microenvironment of the primary tumor plays a key role in tumor cell dissemination and implantation at distant sites. We previously described 2 cancer-associated fibroblasts (CAFs) that either express (CD146+) or lack (CD146–) CD146 (official symbol MCAM, alias MUC18). We now find that when mixed with human breast cancer cells, each fibroblast subtype determines the fate of cancer cells: CD146– fibroblasts promoted increased metastasis compared with CD146+ fibroblasts. Potentially novel quantitative and qualitative proteomic analyses showed that CD146+ CAFs produced an environment rich in basement membrane proteins, while CD146– CAFs exhibited increases in fibronectin 1, lysyl oxidase, and tenascin C, all overexpressed in aggressive disease. We also show clinically that CD146– CAFs predicted for likelihood of lymph node involvement even in small primary tumors (<5 cm). Clearly small tumors enriched for CD146– CAFs require aggressive treatments.
Authors
Heather M. Brechbuhl, Alexander S. Barrett, Etana Kopin, Jaime C. Hagen, Amy L. Han, Austin E. Gillen, Jessica Finlay-Schultz, Diana M. Cittelly, Philip Owens, Kathryn B. Horwitz, Carol A. Sartorius, Kirk Hansen, Peter Kabos
Usage data is cumulative from March 2025 through March 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,091 | 127 |
| 131 | 28 | |
| Figure | 704 | 1 |
| Supplemental data | 76 | 5 |
| Citation downloads | 94 | 0 |
| Totals | 2,096 | 161 |
| Total Views | 2,257 | |
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.
