NATURAL SITE PREFERENCE IN MAMMARY CANCER BIOLOGY

乳腺癌生物学中的自然位点偏好

• 批准号: 3168100
• 负责人: FRED Raymond MILLER
• 金额: $ 13.28万
• 依托单位: BARBARA ANN KARMANOS CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-06-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168100
• 关键词: adipose tissue; breast neoplasms; cancer registry /resource; cell differentiation; collagen; embryo /fetus; extracellular matrix; growth factor; host neoplasm interaction; immunofluorescence technique; intercellular connection; laboratory mouse; laboratory rabbit; lactation; mammary gland; metastasis; mixed tissue /cell culture; mutant; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neoplasm /cancer transplantation; neoplastic growth; neoplastic transformation; preneoplastic state; tissue /cell culture; tissue /cell preparation

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.

我发现小鼠乳腺肿瘤表现出明显的 生长在它们的自然解剖部位，乳房脂肪垫。 此外，发现小鼠乳腺肿瘤更容易转移 而不是皮下组织。 我已经证明， 免疫学机制不能充分解释这些观察到位点 对肿瘤生长和转移的影响，并集中在上皮内 和基质-上皮细胞相互作用作为替代机制。 细胞之间的相互作用的自我平衡机制发生在 胚囊形成 这些监管程序通常能够 在整个生命周期中保持组织完整性， 对肿瘤的“非免疫监视”。 在小鼠中，正常 乳腺组织的相互作用早在 11天（子宫内）胎儿乳芽，处女，期间 妊娠/哺乳相关的腺体重塑，乳房之间 上皮和癌前乳腺组织，以及，如我所示， 正常乳腺组织和恶性乳腺组织。 操纵 组织相互作用的研究可能会导致新的治疗策略， 癌症的生长和进展。 我已经发展出乳腺肿瘤线， 耐药标记，并利用这些来研究代谢 乳腺组织之间的合作。 我已经改编了三维的 培养系统中的胶原蛋白凝胶，研究组织的相互作用，在体外，我 已经开始利用胚胎组织作为一种确定的功能来源， 乳腺间质研究上皮-间充质相互作用与乳腺癌 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部位生长，以确定 地点偏好的机制及其后果。 研究 机制将继续关注细胞内的相互作用 乳腺脂肪垫 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 实验方法基于细胞形状、组织 结构，细胞外基质，以及基质-上皮和 上皮内相互作用可能在正常的 乳腺的生长和发育。