Emerging Biological Principles of Metastasis

Lambert, Arthur W.; Pattabiraman, Diwakar R.; Weinberg, Robert A.

doi:10.1016/j.cell.2016.11.037

Cited by 2,470 publications

(2,328 citation statements)

References 205 publications

(252 reference statements)

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“…Of the patients with a high TSR, 36% were not risk group converted by neoadjuvant treatment and consequently treated post-operatively with adjuvant chemotherapy. The reason for high stroma content being prognostically unfavorable is probably multifaceted, but increasing evidence suggests cellular components of the stroma to be triggering the epithelial-mesenchymal transition in the invasive zone of the tumor and hence increasing the risk of metastatic spread [15].…”

Section: Discussionmentioning

confidence: 99%

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

et al. 2017

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Material and methods: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors were sampled and analyzed by conventional microscopy. Patients were divided into stromahigh (>50%, i.e. TSR low) and stroma-low ( 50%, i.e. TSR high) for the comparison with clinical data. Results: A low TSR was found in 47% of the surgically resected primary tumors and correlated to a significantly higher T-and N-category compared, to tumors with a high TSR (p < .01). A low TSR was also significantly associated with disease recurrence (p ¼ .008), translating into significant differences in disease free survival (DFS) and overall survival, p < .002. The 5-year DFS rate for patients with a low TSR was 55%, compared to 94% in the group of patients with a high TSR. Conclusions: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting patients for post-operative treatment.

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Section: Discussionmentioning

confidence: 99%

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

et al. 2017

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“…2,3 In particular, simultaneously visualizing and quantifying of many components 4 The high mortality of cancer mainly resulted from the poor understanding of cancer invasion and metastasis. [5][6][7] Despite significant advances in gastric cancer (GC) early diagnosis, staging system and treatment, the 5-year overall survival (OS) of GC remains ~40%. 8,9 Extensive evidence across multiple models has verified the critical role for the tumor microenvironment (TME) in promoting tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

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Purpose Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ. Patients and methods A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated. Results This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival ( P <0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup ( P <0.001). Conclusion Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs.

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“…The tumor cells then enter the circulation and exit to colonize a secondary organ and form a metastasis. [20][21][22][23] The mechamisms of the switch from in situ to invasive carcinoma remain largely unknown, although membrane type 1-matrix metalloproteinase (MT1-MMP) is involved in this process. 24,25 The identification of NME1 as the first metastasis suppressor gene 26 has opened the field of this new class of metastasis dissemination regulators ( 27-30 ; Ćetković et al, upcoming issue; 31 Khan and Steeg,32 this issue).…”

Section: Nme In Metastasismentioning

confidence: 99%

The NDPK/NME superfamily: state of the art

Boissan

Schlattner

Lacombe

2018

Laboratory Investigation

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Nucleoside diphosphate kinases (NDPK) are nucleotide metabolism enzymes encoded by NME genes (also called NM23). Given the fact that not all NME-encoded proteins are catalytically active NDPKs and that NM23 generally refers to clinical studies on metastasis, we use here NME/NDPK to denote the proteins. Since their discovery in the 1950's, NMEs/NDPKs have been shown to be involved in multiple physiological and pathological cellular processes, but the molecular mechanisms have not been fully determined. Recent progress in elucidating these underlying mechanisms has been presented by experts in the field at the 10th International Congress on the NDPK/NME/AWD protein family in October 2016 in Dubrovnik, Croatia, and is summarized in review articles or original research in this and an upcoming issue of Laboratory Investigation. Within this editorial, we discuss three major cellular processes that involve members of the multi-functional NME/NDPK family: (i) cancer and metastasis dissemination, (ii) membrane remodeling and nucleotide channeling, and iii) protein histidine phosphorylation.

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Emerging Biological Principles of Metastasis

Cited by 2,470 publications

References 205 publications

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

The NDPK/NME superfamily: state of the art

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