Department of Biological Sciences, Purdue University, West Lafayette, IN 49706, USA.
Int J Cancer. 2013 Jan 15;132(2):288-96. doi: 10.1002/ijc.27672. Epub 2012 Jun 26.
Breast cancer is the most commonly diagnosed cancer among women worldwide. High breast cancer incidence and mortality rates, especially in obese patients, emphasize the need for a better biological understanding of this disease. Previous studies provide substantial evidence for a vital role of the local extracellular environment in multiple steps of tumor progression, including proliferation and invasion. Current evidence supports the role of adipocytes as an endocrine organ, which produces steroid hormones, pro-inflammatory cytokines and adipokines, such as leptin. To further define the role of the mammary microenvironment on tumorigenesis, we have developed an adipose-tumor epithelial cell co-culture system designed to reproduce the in vivo mammary environment. We validate this model through use of coherent anti-Stokes Raman scattering (CARS) microscopy, a label-free vibrational imaging technique. CARS analysis demonstrates the sustained viability of the adipocytes, and that mammary cancer cell morphology parallels that of tumors in vivo. Also, characterized was the influence of mammary adipose tissue on tumor cell growth and migration. Adipose tissue co-cultured with mammary tumor epithelial cells, in the absence of any serum or supplemental growth factors, resulted in substantial increases in growth and migration of tumor cells. In conclusion, this novel co-culture system provides an ideal model to study epithelial-stromal interactions in the mammary gland. Understanding the relationship between adipose tissue, the most abundant and least studied component of the breast stroma and tumor epithelial cells is critical to clarifying the influence of obesity on the development, progression and prognosis of breast cancer.
乳腺癌是全球女性中最常见的癌症。乳腺癌发病率和死亡率高，尤其是在肥胖患者中，这强调了需要更好地了解这种疾病的生物学特性。先前的研究为局部细胞外环境在肿瘤进展的多个步骤中，包括增殖和侵袭，起着至关重要的作用提供了充分的证据。目前的证据支持脂肪细胞作为内分泌器官的作用，它可以产生甾体激素、促炎细胞因子和脂肪因子，如瘦素。为了进一步确定乳腺微环境对肿瘤发生的作用，我们开发了一种脂肪-肿瘤上皮细胞共培养系统，旨在重现体内乳腺环境。我们通过使用无标记的振动成像技术——相干反斯托克斯拉曼散射（CARS）显微镜来验证该模型。CARS 分析表明脂肪细胞的持续活力，并且乳腺癌细胞形态与体内肿瘤的形态相似。此外，还研究了乳腺脂肪组织对肿瘤细胞生长和迁移的影响。在没有任何血清或补充生长因子的情况下，与乳腺肿瘤上皮细胞共培养的脂肪组织导致肿瘤细胞的生长和迁移显著增加。总之，这种新的共培养系统为研究乳腺中上皮-间质相互作用提供了理想的模型。了解脂肪组织（乳腺基质中最丰富但研究最少的成分）与肿瘤上皮细胞之间的关系，对于阐明肥胖对乳腺癌的发展、进展和预后的影响至关重要。
