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Nature Medicine Oct 2011Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is...
Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and β-oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment.
Topics: Adipocytes; Animals; Coculture Techniques; Fatty Acid-Binding Proteins; Female; Humans; Lipid Metabolism; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Omentum; Ovarian Neoplasms; Peritoneal Neoplasms; Tumor Cells, Cultured
PubMed: 22037646
DOI: 10.1038/nm.2492 -
Internal Medicine (Tokyo, Japan) Sep 2020A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum...
A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum between the liver and stomach. Esophagogastroduodenoscopy revealed a submucosal tumor-like change, and endoscopic ultrasonography (EUS) revealed that the mass was located outside of the stomach wall. We performed EUS fine-needle aspiration and diagnosed panniculitis of the lesser omentum. Based on these findings, we suggest that mass-like lesions in the lesser omentum and submucosal tumor-like changes in the anterior wall on the lesser curvature side of the stomach be evaluated for the possibility of panniculitis of the lesser omentum.
Topics: Adult; Biopsy, Fine-Needle; Endosonography; Female; Humans; Omentum; Panniculitis, Peritoneal; Tomography, X-Ray Computed
PubMed: 32461523
DOI: 10.2169/internalmedicine.4300-19 -
JCI Insight Jun 2023The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there...
The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. Studies using CX3CR1-competent and CX3CR1-deficient mice showed that the predominant response in the omentum following saline administration is an accumulation of CX3CR1+ monocytes/macrophages that expand milky spots and promote neoangiogenesis within these niches. Moreover, saline administration promoted the implantation of cancer cells of ovarian and colorectal origin onto the omentum. By contrast, these deleterious effects were not observed following i.p. administration of lactated Ringer's solution. Our findings suggest that normal saline stimulates the receptivity of the omentum for cancer cells and that the risk of colonization can be minimized by using a biocompatible crystalloid for lavage procedures.
Topics: Animals; Mice; Saline Solution; Omentum; Ascitic Fluid; Embryo Implantation; Epithelium
PubMed: 37345662
DOI: 10.1172/jci.insight.167336 -
Journal of Leukocyte Biology Apr 2021The peritoneal cavity is a fluid filled space that holds most of the abdominal organs, including the omentum, a visceral adipose tissue that contains milky spots or... (Review)
Review
The peritoneal cavity is a fluid filled space that holds most of the abdominal organs, including the omentum, a visceral adipose tissue that contains milky spots or clusters of leukocytes that are organized similar to those in conventional lymphoid tissues. A unique assortment of leukocytes patrol the peritoneal cavity and migrate in and out of the milky spots, where they encounter Ags or pathogens from the peritoneal fluid and respond accordingly. The principal role of leukocytes in the peritoneal cavity is to preserve tissue homeostasis and secure tissue repair. However, when peritoneal homeostasis is disturbed by inflammation, infection, obesity, or tumor metastasis, specialized fibroblastic stromal cells and mesothelial cells in the omentum regulate the recruitment of peritoneal leukocytes and steer their activation in unique ways. In this review, the types of cells that reside in the peritoneal cavity, the role of the omentum in their maintenance and activation, and how these processes function in response to pathogens and malignancy will be discussed.
Topics: Adaptive Immunity; Animals; Humans; Immunity; Immunity, Innate; Omentum; Peritoneal Cavity
PubMed: 32881077
DOI: 10.1002/JLB.5MIR0720-271RR -
Shock (Augusta, Ga.) Apr 2020Once thought of as an inert fatty tissue present only to provide insulation for the peritoneal cavity, the omentum is currently recognized as a vibrant immunologic organ... (Review)
Review
Once thought of as an inert fatty tissue present only to provide insulation for the peritoneal cavity, the omentum is currently recognized as a vibrant immunologic organ with a complex structure uniquely suited for defense against pathogens and injury. The omentum is a source of resident inflammatory and stem cells available to participate in the local control of infection, wound healing, and tissue regeneration. It is intimately connected with the systemic vasculature and communicates with the central nervous system and the hypothalamic pituitary adrenal axis. Furthermore, the omentum has the ability to transit the peritoneal cavity and sequester areas of inflammation and injury. It contains functional, immunologic units commonly referred to as "milky spots" that contribute to the organ's immune response. These milky spots are complex nodules consisting of macrophages and interspersed lymphocytes, which are gateways for the infiltration of inflammatory cells into the peritoneal cavity in response to infection and injury. The omentum contains far greater complexity than is currently conceptualized in clinical practice and investigations directed at unlocking its beneficial potential may reveal new mechanisms underlying its vital functions and the secondary impact of omentectomy for the staging and treatment of a variety of diseases.
Topics: Humans; Intraabdominal Infections; Omentum; Wound Healing
PubMed: 31389904
DOI: 10.1097/SHK.0000000000001428 -
The Journal of Experimental Medicine Dec 2021Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly...
Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/- and LYVE1lo/- MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the omentum. Indeed, syngeneic epithelial ovarian tumor growth was strongly reduced following in vivo ablation of LYVE1hi macrophages, including in mice that received omentectomy to dissociate the role from omental macrophages. These data reveal that the peritoneal compartment contains at least four resident macrophage populations and that LYVE1hi mesothelial macrophages drive tumor growth independently of the omentum.
Topics: Animals; Epithelial Cells; Female; Macrophage Colony-Stimulating Factor; Macrophages, Peritoneal; Mice, Inbred C57BL; Mice, Transgenic; Omentum; Ovarian Neoplasms; Peritoneum; Stromal Cells; Transcriptome; Vesicular Transport Proteins; WT1 Proteins; Mice
PubMed: 34714329
DOI: 10.1084/jem.20210924 -
The New England Journal of Medicine Sep 2018
Topics: Abdominal Pain; Adenosine Deaminase; Ascites; Ascitic Fluid; Biopsy; Humans; Mycobacterium tuberculosis; Omentum; Peritoneum; Peritonitis, Tuberculous; Tomography, X-Ray Computed; Young Adult
PubMed: 30231225
DOI: 10.1056/NEJMicm1713168 -
Lakartidningen Nov 2018
Topics: Accidents, Traffic; Female; Humans; Middle Aged; Omentum; Splenosis
PubMed: 30512142
DOI: No ID Found -
Journal of Visceral Surgery Apr 2013
Topics: Humans; Laparotomy; Mediastinitis; Mediastinum; Omentum; Postoperative Complications; Surgical Flaps; Wound Closure Techniques
PubMed: 23582216
DOI: 10.1016/j.jviscsurg.2013.03.009 -
Adipocyte Dec 2019Accumulating evidence highlights the importance of interactions between tumour cells and stromal cells for tumour initiation, progression, and metastasis. In tumours... (Review)
Review
Accumulating evidence highlights the importance of interactions between tumour cells and stromal cells for tumour initiation, progression, and metastasis. In tumours that contain adipocyte in their stroma, adipocytes contribute to modification of tumour microenvironment and affect metabolism of tumour and tumour progression by production of cytokines and adipokines from the lipids. The omentum and bone marrow (BM) are highly adipocyte-rich and are also common metastatic and primary tumour developmental sites. Omental adipocytes exhibit metabolic cross-talk, immune modulation, and angiogenesis. BM adipocytes secrete adipokines, and participate in solid tumour metastasis through regulation of the CCL2/CCR2 axis and metabolic interactions. BM adipocytes also contribute to the progression of hematopoietic neoplasms. Here, we here provide an overview of research progress on the cross-talks between omental/BM adipocytes and tumour cells, which may be pivotal modulators of tumour biology, thus highlighting novel therapeutic targets. MCP-1, monocyte chemoattractant protein 1IL, interleukinSTAT3, signal transducer and activator of transcription 3FABP4, fatty acid binding protein 4PI3K/AKT, phosphoinositide 3-kinase/protein kinase BPPAR, peroxisome proliferator-activated receptorPUFA, polyunsaturated fatty acidTAM, tumour-associated macrophagesVEGF, vascular endothelial growth factorVEGFR, vascular endothelial growth factor receptorBM, bone marrowBMA, bone marrow adipocytesrBMA, regulated BMAcBMA, constitutive BMAUCP-1, uncoupling protein-1TNF-α, tumour necrosis factor-alphaRANKL, receptor activator of nuclear factor kappa-Β ligandVCAM-1, vascular cell adhesion molecule 1JAK2, Janus kinase 2CXCL (C-X-C motif) ligandPGE2, prostaglandin E2COX-2, cyclooxygenase-2CCL2, C-C motif chemokine ligand 2NF-κB, nuclear factor-kappa BMM, multiple myelomaALL, acute lymphoblastic leukemiaAML, acute myeloid leukemiaGDF15, growth differentiation factor 15AMPK, AMP-activated protein kinaseMAPK, mitogen-activated protein kinaseAPL, acute promyelocytic leukemiaCCR2, C-C motif chemokine receptor 2SDF-1α, stromal cell-derived factor-1 alphaFFA, free fatty acidsLPrA, leptin peptide receptor antagonistMCD, malonyl-CoA decarboxylase.
Topics: Adipocytes; Adipokines; Animals; Bone Marrow Cells; Carcinogenesis; Humans; Lipid Metabolism; Omentum; Tumor Microenvironment
PubMed: 31334678
DOI: 10.1080/21623945.2019.1643189