NATURAL SITE PREFERENCE IN MAMMARY CANCER BIOLOGY

我发现小鼠乳腺肿瘤表现出一种显著的偏好 为了在它们的自然解剖部位--乳房肥胖垫中生长。 此外，还发现小鼠乳腺肿瘤更容易转移。 从乳房脂肪垫而不是皮下部位。我已经证明了 免疫机制不能充分解释这些观察到的部位。 对肿瘤生长和转移的影响，并已集中在上皮内 和间质-上皮细胞相互作用作为替代机制。 细胞间相互作用的动态平衡机制 胚泡形成。这些监管程序通常能够 在一生中保持组织的完整性，可以被认为是一种机制 对肿瘤的“非免疫监测”。在小鼠中，正常 乳腺组织的相互作用早在 11天(在子宫内)胎儿乳房发芽，在处女期间 妊娠/哺乳相关腺体重塑，乳房之间 上皮和癌前乳腺组织，以及，如我所示，在 正常乳腺组织和恶性乳腺组织。操纵 组织相互作用可能导致新的治疗策略 癌症的生长和发展。我已经开发出了乳腺肿瘤株 耐药标记物，并利用这些标记物研究代谢 乳腺组织间的配合。我已经改编了三维 胶原凝胶培养体系研究组织相互作用的体外实验 已经开始利用胚胎组织作为确定的功能来源 乳腺间质研究上皮-间充质与乳腺的相互作用 肿瘤细胞。这些新工具将有助于我继续调查 乳腺肿瘤在其自然解剖位置生长以确定 选址偏好的机制及其后果。的研究。 机制将继续专注于 乳腺肥胖症。对后果的研究将集中在 乳腺组织相互作用对肿瘤进展的影响。我的 实验方法基于这样的原理，即细胞形状、组织 建筑，细胞外基质，以及基质上皮和 上皮内相互作用可能都在正常的 乳腺的生长发育。

I have found that mouse mammary tumors demonstrate a remarkable preference for growth in their natural anatomic site, the mammary fatpad. Furthermore, mouse mammary tumors were found to metastasize more readily from the mammary fatpad than from subcutaneous sites. I have shown that immunological mechanisms do not adequately explain these observed site effects on tumor growth and metastasis and have focused on intraepithelial and stromal-epithelial cellular interactions as alternative mechanisms. Interactive homeostatic mechanisms occur between cells from the time of blastlal formation. These regulatory processes are usually able to maintain tissue integrity throughout life and can be regarded as mechanisms of "non-immune surveillance" against neoplasia. In the mouse, normal mammary gland tissue interactions can be demonstrated as early as in the 11\day (in utero) fetal mammary bud, in the virgin female, during pregnancy/lactation related glandular remodeling, between mammary epithelium and preneoplastic mammary tissues, and, as I have shown, between normal mammary gland tissues and malignant mammary tissues. Manipulation of tissue interactions could lead to new therapeutic strategies against cancer growth and progression. I have developed mammary tumor lines with drug resistance markers and have utilized these to study metabolic cooperation between mammary tissues. I have adapted the three-dimensional culture system in collagen gel to study tissue interactions in vitro, and I have begun to utilize embryonic tissues as a defined source of functional mammary mesechyme to study epithelial-mesenchymal interactions with mammary tumor cells. These new tools will aid my continuing investigations of mammary tumors growing in their natural anatomic site to determine both the mechanisms of site preference and their consequences. The study of mechanism will continue to focus on cellular interactions within the mammary gland fatpad. The studies of the consequences will focus on the affect of mammary gland tissue interactions on neoplastic progression. My experimental approaches are based on the principles that cell shape, tissue architecture, the extracellular matrix, and both stromal-epithelial and intraepithelial interactions may all play significant roles in the normal growth and development of the mammary gland.