a Department of Pathology, Yonsei University College of Medicine , Seoul , South Korea.
Adipocyte. 2019 Dec;8(1):304-317. doi: 10.1080/21623945.2019.1643189.
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.
越来越多的证据强调了肿瘤细胞与基质细胞之间相互作用对于肿瘤起始、进展和转移的重要性。在其基质中含有脂肪细胞的肿瘤中，脂肪细胞通过脂质产生细胞因子和脂肪因子来改变肿瘤微环境，并影响肿瘤代谢和肿瘤进展。大网膜和骨髓（BM）富含脂肪细胞，也是常见的转移和原发性肿瘤发育部位。大网膜脂肪细胞表现出代谢串扰、免疫调节和血管生成。BM 脂肪细胞分泌脂肪因子，并通过调节 CCL2/CCR2 轴和代谢相互作用参与实体瘤转移。BM 脂肪细胞也有助于造血肿瘤的进展。在这里，我们概述了大网膜/BM 脂肪细胞与肿瘤细胞之间相互作用的研究进展，这些相互作用可能是肿瘤生物学的关键调节剂，因此强调了新的治疗靶点。MCP-1，单核细胞趋化蛋白 1IL，白细胞介素STAT3，信号转导和转录激活因子 3FABP4，脂肪酸结合蛋白 4PI3K/AKT，磷酸肌醇 3-激酶/蛋白激酶 BPPAR，过氧化物酶体增殖物激活受体PUFA，多不饱和脂肪酸TAM，肿瘤相关巨噬细胞VEGF，血管内皮生长因子VEGFR，血管内皮生长因子受体BM，骨髓BMA，骨髓脂肪细胞rBMA，调节性 BMAcBMA，组成性 BMAUCP-1，解偶联蛋白 1TNF-α，肿瘤坏死因子-αRANKL，核因子 kappa-B 配体受体激活剂VCAM-1，血管细胞黏附分子 1JAK2，Janus 激酶 2CXCL（C-X-C 基序）配体PGE2，前列腺素 E2COX-2，环氧化酶 2CCL2，C-C 基序趋化因子配体 2NF-κB，核因子-kappa BMM，多发性骨髓瘤ALL，急性淋巴细胞白血病AML，急性髓细胞性白血病GDF15，生长分化因子 15AMPK，AMP 激活的蛋白激酶MAPK，丝裂原活化蛋白激酶APL，急性早幼粒细胞白血病CCR2，C-C 基序趋化因子受体 2SDF-1α，基质细胞衍生因子-1αFFA，游离脂肪酸LPrA，瘦素肽受体拮抗剂MCD，丙二酰辅酶 A 脱羧酶。
