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pre metastatic niche

Yang Liu, Xuetao Cao
Primary tumors create a favorable microenvironment, namely, pre-metastatic niche, in secondary organs and tissue sites for subsequent metastases. The pre-metastatic niche can be primed and established through a complex interplay among primary tumor-derived factors, tumor-mobilized bone marrow-derived cells, and local stromal components. We review here our current understanding of the key components and underlying mechanisms for pre-metastatic niche formation. We propose six characteristics that define the pre-metastatic niche, which enable tumor cell colonization and promote metastasis, including immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, and reprogramming...
November 14, 2016: Cancer Cell
Carlo Aprile, Marco G Persico, Lorenzo Lodola, Federica E Buroni
After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization...
October 28, 2016: World Journal of Radiology
Clotilde Dumars, Jean-Michel Ngyuen, Aurélie Gaultier, Rachel Lanel, Nadège Corradini, François Gouin, Dominique Heymann, Marie-Françoise Heymann
Osteosarcoma (OS) is the most common bone sarcoma in adolescents, and has poor prognosis. A vicious cycle is established between OS cells and their microenvironment in order to facilitate the tumor growth and cell spreading. The present work aims to better characterize the tumor microenvironment in OS in order to identify new therapeutic targets relating to metastatic process. Tissue microarrays of pre-chemotherapy OS biopsies were used for characterizing the tumor niche by immunohistochemistry. Parameters studies included: immune cells (M1, M2-subtypes of tumor-associated macrophages (TAM); T, B lymphocytes; mast cells), vascularization (endothelial, perivascular cells), OPG, RANKL, and mitotic index...
November 13, 2016: Oncotarget
Pnina Brodt
Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal tract but also for other malignancies, such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between tumor cells and different local resident subpopulations, including the sinusoidal endothelium, stellate, Kupffer, and inflammatory cells that are mediated through cell-cell and cell-extracellular matrix adhesion and the release of soluble factors...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Marlana Orloff
On October 27, 2015, talimogene laherparepvec (T-VEC), a first in class intralesional oncolytic virotherapy, was granted the US Food and Drug Administration approval for the treatment of melanoma in the skin and lymph nodes. Its approval has added yet another therapeutic option to the growing list of effective therapies for melanoma. Though the Phase III OPTiM trial has demonstrated its efficacy as a single agent, the target patient population remains narrow. With numerous effective and tolerable treatments available for unresectable and metastatic melanoma, intralesional therapies such as T-VEC are still finding their niche...
2016: Oncolytic Virotherapy
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
Alison Gartland, Janine T Erler, Thomas R Cox
Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour...
September 2016: Journal of Bone Oncology
Zhipeng Chen, Lijuan Yang, Yizhi Cui, Yanlong Zhou, Xingfeng Yin, Jiahui Guo, Gong Zhang, Tong Wang, Qing-Yu He
The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines...
September 1, 2016: Oncotarget
E E Mowers, M N Sharifi, K F Macleod
Autophagy is a highly conserved self-degradative process that has a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at nearly every phase of the metastatic cascade has been identified...
September 5, 2016: Oncogene
Barbara Grünwald, Veronika Harant, Susanne Schaten, Monika Frühschütz, Ria Spallek, Bastian Höchst, Katharina Stutzer, Sonja Berchtold, Mert Erkan, Olga Prokopchuk, Marc Martignoni, Irene Esposito, Mathias Heikenwalder, Aayush Gupta, Jens Siveke, Paul Saftig, Percy Knolle, Dirk Wohlleber, Achim Krüger
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) metastasizes to liver at early stages, making this disease highly lethal. Tissue inhibitor of metalloproteinases-1 (TIMP1) creates a metastasis-susceptible environment in the liver. We investigated the role of TIMP1 and its receptor CD63 in metastasis of early-stage pancreatic tumors using mice and human cell lines and tissue samples. METHODS: We obtained liver and plasma samples from patients in Germany with chronic pancreatitis, pancreatic intra-epithelial neoplasia, or PDAC, as well as hepatic stellate cells (HSCs)...
August 6, 2016: Gastroenterology
Yanfang Liu, Yan Gu, Yanmei Han, Qian Zhang, Zhengping Jiang, Xiang Zhang, Bo Huang, Xiaoqing Xu, Jianming Zheng, Xuetao Cao
The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models...
August 8, 2016: Cancer Cell
Candia M Kenific, Laura Nogués, David Lyden
Pre-Metastatic Niches (PMNs) result from communications between primary tumors and the microenvironment of future distant metastasis via tumor-derived factors. In this issue of Cancer Cell, Liu et al. show that TLR3 activation in lung epithelial cells by tumor exosomal RNAs triggers neutrophil recruitment, which contributes to PMN formation and metastasis.
August 8, 2016: Cancer Cell
Megumu Tanaka, Teruhide Koyama, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Tian Liu, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Shinji Owa, Akihiro Yamauchi, Kyoko Igarashi, Shun'ichiro Taniguchi, Takayuki Shindo
AIMS: Controlling vascular integrity is expected to be a novel therapeutic target of cancers as well as cardiovascular diseases. Adrenomedullin (AM) and its receptor-modulating protein, RAMP2, have been identified as essential mediators of cardiovascular homeostasis. In this study, we used inducible vascular endothelial cell-specific RAMP2 knockout (DI-E-RAMP2(-/-)) mice to clarify the contribution made by the endogenous AM-RAMP2 system to angiogenesis and metastasis. METHODS AND RESULTS: Subcutaneously transplanted sarcoma or melanoma cells showed less growth and angiogenesis in DI-E-RAMP2(-/-) than in control mice...
September 2016: Cardiovascular Research
Salvatore Grisanti, Alessandro Antonelli, Michela Buglione, Camillo Almici, Chiara Foroni, Mario Sodano, Luca Triggiani, Diana Greco, Carlotta Palumbo, Mirella Marini, Stefano M Magrini, Alfredo Berruti, Claudio Simeone
BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence...
June 2016: Anticancer Research
Rebecca A Barnard, Daniel P Regan, Ryan J Hansen, Paola Maycotte, Andrew Thorburn, Daniel L Gustafson
The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases. Similarly, autophagy inhibition by adjuvant chloroquine (CQ) treatment did not delay metastasis in an orthotopic 4T1, tumor-resection model...
August 2016: Journal of Pharmacology and Experimental Therapeutics
Zhe Wang, Shanshan Xiong, Yubin Mao, Mimi Chen, Xiaohong Ma, Xueliang Zhou, Zhenling Ma, Fan Liu, Zhengjie Huang, Qi Luo, Gaoliang Ouyang
Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites...
August 2016: Journal of Pathology
Yongfeng Zhao, Lisa Detering, Deborah Sultan, Matthew L Cooper, Meng You, Sangho Cho, Stephanie L Meier, Hannah Luehmann, Guorong Sun, Michael Rettig, Farrokh Dehdashti, Karen L Wooley, John F DiPersio, Yongjian Liu
As an emerging class of nanomaterial, nanoclusters hold great potential for biomedical applications due to their unique sizes and related properties. Herein, we prepared a (64)Cu doped gold nanocluster ((64)CuAuNC, hydrodynamic size: 4.2 ± 0.5 nm) functionalized with AMD3100 (or Plerixafor) for targeted positron emission tomography (PET) imaging of CXCR4, an up-regulated receptor on primary tumor and lung metastasis in a mouse 4T1 orthotopic breast cancer model. The preparation of targeted (64)CuAuNCs-AMD3100 (4...
June 28, 2016: ACS Nano
I Made Winarsa Ruma, Endy Widya Putranto, Eisaku Kondo, Hitoshi Murata, Masami Watanabe, Peng Huang, Rie Kinoshita, Junichiro Futami, Yusuke Inoue, Akira Yamauchi, I Wayan Sumardika, Chen Youyi, Ken-Ichi Yamamoto, Yasutomo Nasu, Masahiro Nishibori, Toshihiko Hibino, Masakiyo Sakaguchi
The dynamic interaction between tumor cells and their microenvironment induces a proinflammatory milieu that drives cancer development and progression. The S100A8/A9 complex has been implicated in chronic inflammation, tumor development, and progression. The cancer microenvironment contributes to the up-regulation of this protein complex in many invasive tumors, which is associated with the formation of pre-metastatic niches and poor prognosis. Changing adhesive preference of cancer cells is at the core of the metastatic process that governs the reciprocal interactions of cancer cells with the extracellular matrices and neighboring stromal cells...
August 2016: Clinical & Experimental Metastasis
Phillip Munson, Arti Shukla
Exosomes are membrane-bound, intercellular communication shuttles that are defined by their endocytic origin and size range of 30-140 nm. Secreted by nearly all mammalian cell types and present in myriad bodily fluids, exosomes confer messages between cells, proximal and distal, by transporting biofunctional cargo in the form of proteins, nucleic acids, and lipids. They play a vital role in cellular signaling in both normal physiology and disease states, particularly cancer. Exosomes are powerful progenitors in altering target cell phenotypes, particularly in tumorigenesis and cancer progression, with the ability to alter tumor microenvironments and to assist in establishing the pre-metastatic niche...
December 2015: Medicines (Basel, Switzerland)
Anette M Høye, Janine T Erler
The aim of this review is to give an overview of the extracellular matrix (ECM) components that are important for creating structural changes in the premetastatic and metastatic niche. The successful arrival and survival of cancer cells that have left the primary tumor and colonized distant sites depends on the new microenvironment they encounter. The primary tumor itself releases factors into the circulation that travel to distant organs and then initiate structural changes, both non-enzymatic and enzymatic, to create a favorable niche for the disseminating tumor cells...
June 1, 2016: American Journal of Physiology. Cell Physiology
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