Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors.
Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors.
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DOI：
10.1158/1078-0432.ccr-11-1916
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Kolonin MG
中科院分区：
文献类型：
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作者：
Klopp AH;Zhang Y;Solley T;Amaya-Manzanares F;Marini F;Andreeff M;Debeb B;Woodward W;Schmandt R;Broaddus R;Lu K;Kolonin MG
脂肪组织含有一群嗜肿瘤的间充质祖细胞，称为脂肪基质细胞（ASC），其在邻近肿瘤中移植以形成支持性肿瘤基质。我们假设，腹腔内内脏脂肪组织可能含有一个独特的肿瘤促进人口的ASC占多余的内脏脂肪组织和腹腔内癌症的死亡率之间的关系。为了研究这一点，我们从腹腔内大网膜脂肪组织（O-ASC）中分离并鉴定了ASC，并与皮下脂肪来源的间充质基质细胞（SC-ASC）、骨髓来源的间充质基质细胞（BM-MSC）相比，鉴定了它们对子宫内膜癌进展的影响。和肺成纤维细胞。为了模拟肿瘤对ASC的慢性募集，将细胞按节拍注射到携带Hec 1a异种移植物的小鼠中。O-ASC表达BM-MSC特征性的细胞表面标志物并分化为间充质谱系。与O-ASC共培养增加了子宫内膜癌细胞的体外增殖。O-ASC和SC-ASC对人Hec 1a子宫内膜肿瘤异种移植物的肿瘤嗜性相当，但O-ASC更有效地促进肿瘤生长。与SC-ASC注射小鼠的肿瘤相比，O-ASC注射小鼠的肿瘤含有更多数量的大曲折结蛋白阳性血管，这与中央肿瘤坏死减少和肿瘤细胞增殖增加相关。O-ASC-表现出增强的运动性相比，SC-ASC在响应Hec 1a分泌的因子。内脏脂肪中含有多能MSC，其促进子宫内膜肿瘤生长的作用比皮下脂肪组织中的MSC更强。我们认为，O-ASC募集到肿瘤表达的特定因子，增强肿瘤血管化，促进肿瘤细胞的存活和增殖。
Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers. To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared to subcutaneous adipose derived mesenchymal stromal cells (SC-ASC), bone marrow derived mesenchymal stromal cells (BM-MSC) and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts. O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Co-culture with O-ASC increased endometrial cancer cell proliferation in-vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC-injected mice, tumors in O-ASC-injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC-exhibited enhanced motility as compared to SC-ASC in response to Hec1a secreted factors. Visceral adipose contains a population of multipotent MSC that promote endometrial tumor growth more potently than MSC from subcutaneous adipose tissue. We propose that O-ASC recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells.