Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2012 Feb 1;18(3):771-82. doi: 10.1158/1078-0432.CCR-11-1916. Epub 2011 Dec 13.
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 with 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. Coculture 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 with SC-ASC in response to Hec1a-secreted factors.
Visceral adipose tissue contains a population of multipotent MSCs that promote endometrial tumor growth more potently than MSCs from subcutaneous adipose tissue. We propose that O-ASCs recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells.
脂肪组织中存在一群肿瘤趋向性的间充质祖细胞，称为脂肪基质细胞（ASC），它们植入邻近的肿瘤中形成支持性肿瘤基质。我们假设，腹腔内脏脂肪组织可能含有一群独特的促进肿瘤生长的 ASC，以解释过多的内脏脂肪组织与腹腔内癌症死亡率之间的关系。
为了研究这一点，我们从腹腔大网膜脂肪组织（O-ASC）中分离和鉴定了 ASC，并将其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）和肺成纤维细胞进行比较，以研究它们对子宫内膜癌进展的影响。为了模拟 ASC 被肿瘤慢性招募的情况，我们将细胞以节拍式方式注射到荷有人 Hec1a 异种移植瘤的小鼠体内。
O-ASC 表达了 BM-MSC 的特征性细胞表面标志物，并分化为间充质谱系。与 O-ASC 共培养可增加子宫内膜癌细胞在体外的增殖。O-ASC 和 SC-ASC 对人 Hec1a 子宫内膜肿瘤异种移植瘤的肿瘤趋向性相似，但 O-ASC 更能促进肿瘤生长。与 SC-ASC 注射小鼠的肿瘤相比，O-ASC 注射小鼠的肿瘤中含有更多数量的大而扭曲的结蛋白阳性血管，这与中心肿瘤坏死减少和肿瘤细胞增殖增加有关。与 SC-ASC 相比，O-ASC 对 Hec1a 分泌因子的反应表现出更强的迁移能力。
内脏脂肪组织中含有一群多能 MSC，它们比皮下脂肪组织中的 MSC 更能促进子宫内膜肿瘤的生长。我们提出，募集到肿瘤中的 O-ASC 表达特定的因子，增强肿瘤血管生成，促进肿瘤细胞的存活和增殖。
