Tumor Metastasis: Molecular Insights and Evolving Paradigms

Published on Oct 14, 2011in Cell38.637
· DOI :10.1016/J.CELL.2011.09.024
Scott Valastyan10
Estimated H-index: 10
(MIT: Massachusetts Institute of Technology),
Robert A. Weinberg198
Estimated H-index: 198
(MIT: Massachusetts Institute of Technology)
Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting.
Figures & Tables
📖 Papers frequently viewed together
3,537 Citations
7,070 Citations
3,153 Citations
#1Lucia Ricci-Vitiani (ISS: Istituto Superiore di Sanità)H-Index: 41
#2Roberto Pallini (Sapienza University of Rome)H-Index: 47
Last. Ruggero De Maria (ISS: Istituto Superiore di Sanità)H-Index: 61
view all 11 authors...
This is one of two papers showing that glioblastoma cells can differentiate into functional endothelial cells as part of the tumour vasculature. These endothelial cells are characterized by the same genetic alterations as the glioblastoma cells. The tumour-derived endothelial cells originate in putative glioblastoma-initiating cells and are functionally important for tumorigenesis.
1,028 CitationsSource
#1Bin-Zhi Qian (Albert Einstein College of Medicine)H-Index: 20
#2Jiufeng Li (Albert Einstein College of Medicine)H-Index: 8
Last. Jeffrey W. Pollard (Albert Einstein College of Medicine)H-Index: 108
view all 9 authors...
Macrophages are abundant in tumours, where they promote tumorigenesis and metastasis. Jeffrey Pollard and colleagues now identify inflammatory monocytes as a precursor population for the macrophages that promote breast cancer metastasis to the lung or bone. These cells are recruited through the cytokine CCL2 and promote tumour-cell extravasation (by producing the signal protein VEGF) and the seeding of metastases. These findings can explain the poor prognosis for breast cancer patients with elev...
1,633 CitationsSource
#1Jacky G. Goetz (Centro Nacional de Investigaciones Cardiovasculares)H-Index: 28
#2Susana Minguet (Centro Nacional de Investigaciones Cardiovasculares)H-Index: 24
Last. Miguel A. del Pozo (Centro Nacional de Investigaciones Cardiovasculares)H-Index: 35
view all 17 authors...
Summary Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190R...
497 CitationsSource
#1Marcin P. Iwanicki (Harvard University)H-Index: 21
#2Rachel A. Davidowitz (Harvard University)H-Index: 4
Last. Joan S. Brugge (Harvard University)H-Index: 122
view all 9 authors...
Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance. H...
194 CitationsSource
#1Thordur Oskarsson (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 23
#2Swarnali Acharyya (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 15
Last. Joan Massagué (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 202
view all 10 authors...
Tenascin C is an extracellular matrix protein previously linked to breast cancer metastasis. Here the authors uncover how tenascin C promotes the fitness of metastasis-initiating cells by sustaining the stem and survival signaling pathways NOTCH and Wnt through specific regulation of Msi1 and Lgr5, respectively.
626 CitationsSource
#1Katherine N. Weilbaecher (WashU: Washington University in St. Louis)H-Index: 47
#2Theresa A. Guise (IU: Indiana University)H-Index: 67
Last. Laurie K. McCauley (UM: University of Michigan)H-Index: 72
view all 3 authors...
When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and in...
809 CitationsSource
#1Peter Carmeliet (Katholieke Universiteit Leuven)H-Index: 181
#2Rakesh K. Jain (Harvard University)H-Index: 210
Vessel normalization strategies aim to increase tumour perfusion and oxygenation, and have the potential to reduce metastasis and improve responses to conventional anticancer therapies. Here, Carmeliet and Jain discuss the benefits and limitations of this emerging new treatment paradigm for cancer and other angiogenic disorders.
1,071 CitationsSource
#1Heidi Schwarzenbach (UHH: University of Hamburg)H-Index: 41
#2Dave S.B. HoonH-Index: 99
Last. Klaus Pantel (UHH: University of Hamburg)H-Index: 128
view all 3 authors...
1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4
1,899 CitationsSource
#1Monte M. Winslow (MIT: Massachusetts Institute of Technology)H-Index: 40
#2Talya L. Dayton (MIT: Massachusetts Institute of Technology)H-Index: 17
Last. Tyler Jacks (MIT: Massachusetts Institute of Technology)H-Index: 158
view all 16 authors...
In a mouse model of lung cancer driven by activated K-Ras and p53 loss, Jacks and colleagues describe a method for tracing individual metastases back to the primary tumours, allowing non-metastatic lesions to be distinguished from metastatic lesions in the same animal. A comparison of gene-expression signatures between metastatic and non-metastatic tumours with human lung cancers led to the identification of Nkx2-1/TTF-1 as a gene that is down-regulated during tumour progression in mice, and ass...
319 CitationsSource
#3Davide Moi (UniSR: Vita-Salute San Raffaele University)H-Index: 11
Summary Tumor-infiltrating myeloid cells convey proangiogenic programs that counteract the efficacy of antiangiogenic therapy. Here, we show that blocking angiopoietin-2 (ANG2), a TIE2 ligand and angiogenic factor expressed by activated endothelial cells (ECs), regresses the tumor vasculature and inhibits progression of late-stage, metastatic MMTV-PyMT mammary carcinomas and RIP1-Tag2 pancreatic insulinomas. ANG2 blockade did not inhibit recruitment of MRC1 + TIE2-expressing macrophages (TEMs) b...
449 CitationsSource
Cited By2367
#1Yuan LiuH-Index: 1
#2Nana LyuH-Index: 2
Last. Yuling WangH-Index: 49
view all 4 authors...
#1Chunmei Lai (FZU: Fuzhou University)
#2Simin Lin (FZU: Fuzhou University)
Last. Yanqiao Jin (FZU: Fuzhou University)H-Index: 1
view all 4 authors...
Abstract null null Carbon quantum dots (CQDs), a new type of fluorescence carbon nanomaterials with particle size varied from 2 to 10 nm, have attracted much attention due to their strong multi-color luminescence properties, unprecedented biocompatibility, excellent aqueous dispersibility and easy preparation from a wide range of carbon materials. These multiple attributes help CQDs possess a broad range of prospective applications in numerous fields, especially for bio-imaging, drug delivery, c...
#1Sijia SunH-Index: 5
#2Min Jo KimH-Index: 4
Last. Suresh AwaleH-Index: 38
view all 5 authors...
#1Mengya Chen (USST: University of Shanghai for Science and Technology)H-Index: 6
#2Yule Zhang (USST: University of Shanghai for Science and Technology)H-Index: 4
Last. Dawei Zhang (USST: University of Shanghai for Science and Technology)H-Index: 58
view all 11 authors...
Abstract Multifunctional nanoplatforms for the early diagnosis and precise treatment of cancers have been widely explored in nanomedicine but still suffer from complex material design and intrinsic incompatibility among various biomaterial components. Moreover, a rational mode of tumor therapy that considers the effect of immune adjuvants while promoting long-term cancer immunotherapy is highly needed. Herein, we developed smart metal-free two-dimensional (2D) graphitic carbon nitride/chlorin e6...
#1Shengchen Lin (PSU: Pennsylvania State University)H-Index: 8
#2Yunzhan Li (PSU: Pennsylvania State University)
Last. Gina M. DeNicolaH-Index: 23
view all 13 authors...
Abstract null null Fascin is a pro-metastatic actin-bundling protein that is upregulated in all metastatic carcinomas. Fascin promotes cancer cell migration and invasion by facilitating membrane protrusions, such as filopodia and invadopodia. Aerobic glycolysis is a key feature of cancer metabolism and provides critical intermediate metabolites for tumor growth. Here, we report that fascin increases glycolysis in lung cancer to promote tumor growth and metastasis. Fascin promotes glycolytic flux...
1 CitationsSource
#1Takeharu Sakamoto (Kansai Medical University)
#2Yuya Fukui (Kanazawa University)
Last. Jun-ichiro Inoue (UTokyo: University of Tokyo)H-Index: 74
view all 13 authors...
Hypoxia-inducible factor-1 (HIF-1) plays essential roles in human diseases, though its central role in oxygen homoeostasis hinders the development of direct HIF-1-targeted pharmacological approaches. Here, we surveyed small-molecule compounds that efficiently inhibit the transcriptional activity of HIF-1 without affecting body homoeostasis. We focused on Mint3, which activates HIF-1 transcriptional activity in limited types of cells, such as cancer cells and macrophages, by suppressing the facto...
#1Lubiao Liang (Zunyi Medical College)
#2Ran Sui (Chongqing University)
Last. Yajin Zhao (Zunyi Medical College)
view all 4 authors...
Tumor acidic microenvironment is the main feature of many solid tumors. As a part of the tumor microenvironment, it has a profound impact on the occurrence and development of tumors. However, the research on how tumor cells sense the changes of the external microenvironment and how the intracellular subcellular structures transmit the signals from extracellular to intracellular is unclear. In this study, we identify that the acidic microenvironment enhances cancer cell motility, and the expressi...
Last. Svetlana P. ErmakovaH-Index: 30
view all 7 authors...
Colorectal cancer is one of the most frequent types of malignancy in the world. The search for new approaches of increasing the efficacy of cancer therapy is relevant. This work was aimed to study individual, combined anticancer effects, and molecular mechanism of action of sulfated laminaran AaLs of the brown alga Alaria angusta and protolinckiosides A (PL1), B (PL2), and linckoside L1 (L1) of the starfish Protoreaster lincki using a 3D cell culture model. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-...
Previously, we showed that mice treated with cyclophosphamide (CTX) 4 days before intravenous injection of breast cancer cells had more cancer cells in the lung at 3 h after cancer injection than control counterparts without CTX. At 4 days after its injection, CTX is already excreted from the mice, allowing this pre-treatment design to reveal how CTX may modify the lung environment to indirectly affect cancer cells. In this study, we tested the hypothesis that the increase in cancer cell abundan...
#1Shuo Ma (Nantong University)H-Index: 1
#2Xinliang Gu (Nantong University)H-Index: 1
Last. Shaoqing Ju (Nantong University)H-Index: 17
view all 7 authors...
Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro ex...