Omentum and bone marrow: how adipocyte‐rich organs create tumour microenvironments conducive for metastatic progression

Gusky, Halina Chkourko; Diedrich, Jonathan D.; MacDougald, Ormond A.; Podgorski, Izabela

doi:10.1111/obr.12450

Cited by 50 publications

(37 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adiponectin, interleukin-6, interleukin-8, C-X-C motif chemokine ligand 1 and others derived from omental adipocytes support the survival and dissemination of tumor cells to regions with increased levels of inflammatory cells [102][103][104]. OC cells regulate adipocyte fatty acid metabolism and the transfer of lipids from adipocytes to tumour cells, which enhances beta fatty acid oxidation and tumour cell proliferation [104][105][106].…”

Section: Metastases and Tumour Microenvironment In Ocmentioning

confidence: 99%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

View full text Add to dashboard Cite

Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease. of 35have been observed in OC patients but not in patients with benign and borderline tumours, and this hypomethylation correlates with advanced-stage disease and poor prognosis [48,49]. A genome-wide methylation profiling of blood cells from healthy controls and age-matched untreated OC patients identified CpG methylation of 2714 cancer-related genes, of which 56% were hypomethylated [50]. Ovarian Cancer Stem CellsCellular heterogeneity associated with genetic and epigenetic changes in tumours are linked with the initiation and expansion of CSCs, a population of cells within the tumour, which initiate tumour growth through self-renewal and differentiation processes [51,52]. These cells are more adaptive to the changing tumour microenvironment and tend to be more resistant to treatment. CSCs are highly plastic and a few numbers of isolated CSCs have been shown to be responsible for tumorgenesis and are more chemotherapy and radiation resistant due to their dormant state and a high expression of drug efflux pumps [53,54]. As a result, CSCs are able to adapt to different tumour microenvironments and survive due to their efficient DNA repair mechanisms and their capacity to evade host immune surveillance [55][56][57]. These inherent properties of CSCs suggest an active role in tumour relapse and emphasize the need to develop effective targeted therapies to improve clinical outcomes in patients [51][52][53][54][55][56][57].Stem cells have been identified in ovaries and fallopian tubes [58,59]. These cells express proteins including aldehyde dehydrogenase family 1 A2 (ALDH1A2), homeobox protein NANOG, LIM homeobox protein 9 (LHX9) and frizzled-related protein 1 (SRFP1) and have been observed in OSE, CIC and fimbria [2,[58][59][60][61][62]. In a...

show abstract

Section: Metastases and Tumour Microenvironment In Ocmentioning

confidence: 99%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…transfer of cells , in our experiments we have observed no CFSE‐labelled donor cells in these localizations (data not shown). Contrary to this, significant CFSE + cell aggregates were present in the omental milky spots, which were already described as gateways for trafficking of B2‐B cells , dendritic cells and preferential sites for tumour cell adhesion (reviewed in ). The morphology of milky spots resembles that of secondary lymphoid organs; however, they are covered by a discontinuous layer of mesothelial cells .…”

Section: Discussionmentioning

confidence: 88%

Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes

Kugyelka

Kohl

Olasz

et al. 2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

The tyrosine kinase zeta chain-associated protein of 70 kDa (ZAP-70) plays a key role in T cell development and signalling. In the absence of ZAP-70, T cell development is arrested in the CD4 CD8 double-positive stage, thus ZAP-70 homozygous knockout (ZAP-70 ) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency. We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70 mice. We used a single intraperitoneal (i.p.) injection to deliver donor thymocytes to the recipients. Here, we show that after i.p. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where donor-originated CD4 CD8 double-negative thymocytes most probably restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70 mice as late as 8 months after i.p. injection. We demonstrate that a simple i.p. injection of ZAP-70 thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70-deficient mice.

show abstract

“…Accelerated bone remodeling is one of the key factors associated with reactivation and growth of tumor cells colonized in the bone. Experimental treatment-induced osteoclasts formation and bone resorption, in turn, increase tumor cell growth and occurrences of bone metastases ( 128 ).…”

Section: Bmas and Mechanisms Responsible For Macrometastasis And Outgmentioning

confidence: 99%

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Liu

Zhao

2020

Front. Oncol.

View full text Add to dashboard Cite

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

show abstract

Omentum and bone marrow: how adipocyte‐rich organs create tumour microenvironments conducive for metastatic progression

Cited by 50 publications

References 159 publications

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Contact Info

Product

Resources

About