ArticlePLoS biology2014
Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 152 citations in OpenAlex.
- Tissue flow acts as a guidance cue for immune cell polarization and directional migration.Nature cell biology · 2026Article
- A 3D model to evaluate cell chemotaxis within a heterogenic tumor microenvironment.Lab on a chip · 2026Article
- Beyond the chaos: How architecture structures tumour biology.The FEBS journal · 2026Review
- Chemical and Mechanical Regulation of Leukocyte Migration.Cold Spring Harbor perspectives in biology · 2026Review
- Macrophages self-generate and refine chemotactic gradients during migration towards complement C5a.PLoS biology · 2026Article
- Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets.International journal of molecular sciences · 2026Review
- Modeling feasible locomotion of nanobots for cancer detection and treatment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- Nongenetic adaptation by collective migration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dynamic cluster field modeling of collective chemotaxis.Scientific reports · 2024Article
- Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.Developmental cell · 2024Article
- EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake.eLife · 2024Article
- pH-regulated single cell migration.Pflugers Archiv : European journal of physiology · 2024Review
- G protein-coupled receptors: a gateway to targeting oncogenic EVs?Extracellular vesicles and circulating nucleic acids · 2024Review
- Chemotaxis Assay of Bone Marrow-Derived Macrophages.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Tumour follower cells: A novel driver of leader cells in collective invasion (Review).International journal of oncology · 2023Review
- Multi-level integrative analysis of the roles of lncRNAs and differential mRNAs in the progression of chronic pancreatitis to pancreatic ductal adenocarcinoma.BMC genomics · 2023Article
- Tumor spheroids accelerate persistently invading cancer cells.Scientific reports · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.