PESO: Materials and Multivariable Models to Predict Tissue Tropism in Metastasis

PESO：预测转移组织向性的材料和多变量模型

• 批准号: 1234852
• 负责人: Shelly Peyton
• 金额: $ 59万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1234852&HistoricalAwards=false
• 关键词: PESO; Materials; Multivariable; Models; Predict

This PESO award to University of Massachusetts at Amherst by the Biomaterials program in the Division of Materials Research is cofunded by the Biotechnology, Biochemical, Biomass Engineering Program (ENG/CBET); the Materials and Surface Engineering program (ENG/CMMI); and the Office of Physical Sciences-Oncology (OPSO) of the National Cancer Institute. Metastasis is the leading cause of fatality for women diagnosed with breast cancer. The most common tissue sites of distant tumor growth in breast cancer include the brain, lung, liver, and bone. Given the clear diversity of the biophysical properties of these distant tissue sites, this proposal hypothesizes that the physical and chemical properties of these tissues regulate the ability of cancer cells to migrate and proliferate, the two critical steps for the metastatic lesion formation. The objectives of this proposal include: 1) the development of 3D biomaterials, which can be engineered to capture physical and chemical factors of the extracellular matrix of these tissue sites (brain, lung, and bone); 2) quantification of how a variety of distinct human breast cancer cell lines migrate and proliferate in response to these physical and chemical cues; and 3) use of statistical modeling tools to both describe and predict the relationship between the tunable biomaterials cues, the signaling network within human breast cancer cell lines, and the ability of cancer cells to migrate and proliferate in these 3D tunable biomaterials. The results of these objectives will establish a new class of biomaterials in which to systematically study how the extracellular matrix impacts breast cancer metastasis, as well as gain fundamental knowledge of how biophysical tissue properties impact the biology of cancer metastasis. As part of the outreach activities, the project plans to initiate a summer research program for female high school students and teachers in collaboration with the diversity program at the campus. The PIs have also proposed to develop plans on how to evaluate the success of educational and outreach program, and how to improve them.Most of the breast cancer deaths are linked to metastasis: the ability of cancer cells to leave the primary tumor site and spread to other organs. One of the roadblocks holding back progress is that the vast majority of breast cancer research is performed with cells cultured on plastic or glass surfaces, which are flat, incredibly rigid, and behave nothing like the complex, three-dimensional, comparatively soft tissues in the human body. For this reason, this project is in developing novel environments that look, and functionally behave like actual human tissue. With this award, 3D structures in a tissue-like environment that will be prepared to make breast cancer cells think that they are in a real tumor tissue, or tissues that breast cancer cells most frequently metastasize to such as the bone, lung, and brain. Using these novel tissue-like systems, this project will study how metastatic breast cancer cells sense and respond to these distant tissue sites, and why certain breast cancer cells prefer to spread to one organ versus another. It is well known that each breast cancer patient is unique, and the preference for cancer to spread to certain organs is patient-specific. For this reason, this project will investigate cells from many different breast cancer disease subtypes, to learn why this cancer spread is patient-specific. The project envisions that these novel tools will radically change how the cancer field studies metastasis, and by using materials that behave more like human tissue, much more rapid progress could be made possible toward the development of useful chemotherapy drugs. As part of this grant proposal, this investigator is partnering with the Diversity Program Office at the campus to form an educational outreach program titled 'Engineering the Cell: A Bioengineering Experience for Young Women' targeting high school teachers and female students. This program will integrate research and education by training both students and teachers in a laboratory setting, and allowing teachers to take laboratory modules back with them to the classroom for curriculum development. Successful implementation and growth of this program will be one mechanism by which to increase the participation of women in bioengineering and related scientific fields.

该比索奖由材料研究部的生物材料计划授予马萨诸塞大学阿默斯特分校，由生物技术、生化、生物量工程计划(ENG/CBET)、材料和表面工程计划(ENG/CMMI)以及国家癌症研究所的物理科学-肿瘤学办公室(OPSO)共同资助。转移是被诊断为乳腺癌的妇女死亡的主要原因。乳腺癌中最常见的远处肿瘤生长组织部位包括脑、肺、肝和骨。鉴于这些远距离组织部位的生物物理性质的明显多样性，这一建议假设这些组织的物理和化学性质调节癌细胞的迁移和增殖能力，这是转移病变形成的两个关键步骤。这项建议的目标包括：1)开发3D生物材料，这种材料可以被设计成捕捉这些组织部位(脑、肺和骨)细胞外基质的物理和化学因素；2)量化各种不同的人类乳腺癌细胞系如何响应这些物理和化学线索迁移和增殖；以及3)使用统计建模工具来描述和预测可调生物材料线索、人类乳腺癌细胞系内的信号网络和癌细胞在这些3D可调生物材料中迁移和增殖的能力之间的关系。这些目标的结果将建立一类新的生物材料，在其中系统地研究细胞外基质如何影响乳腺癌转移，以及获得关于生物物理组织特性如何影响癌症转移生物学的基础知识。作为外联活动的一部分，该项目计划与校园多样性方案合作，为女高中生和教师发起暑期研究方案。PIs还建议制定计划，以评估教育和外展计划的成功，以及如何改进它们。大多数乳腺癌死亡与转移有关：癌细胞离开原发肿瘤部位并扩散到其他器官的能力。阻碍进展的一个障碍是，绝大多数乳腺癌研究是在塑料或玻璃表面上培养的细胞进行的，塑料或玻璃表面是平的，非常坚硬，表现与人体复杂的三维相对软组织完全不同。出于这个原因，这个项目正在开发新的环境，看起来和功能上都像真正的人体组织。有了这一奖项，在类似组织的环境中的3D结构将准备使乳癌细胞认为它们位于真实的肿瘤组织中，或乳癌细胞最常转移到的组织中，如骨、肺和脑。使用这些新的组织状系统，这个项目将研究转移性乳腺癌细胞如何感知和响应这些远处的组织部位，以及为什么某些乳腺癌细胞更喜欢扩散到一个器官而不是另一个器官。众所周知，每个乳腺癌患者都是独一无二的，而且癌症扩散到特定器官的偏好是患者特有的。出于这个原因，这个项目将研究来自许多不同乳腺癌疾病亚型的细胞，以了解为什么这种癌症扩散是患者特有的。该项目设想，这些新工具将从根本上改变癌症领域研究转移的方式，通过使用更像人体组织的材料，可以在开发有用的化疗药物方面取得更快的进展。作为这项拨款提案的一部分，这位研究人员正在与校园内的多样性项目办公室合作，形成一个名为“设计细胞：年轻女性的生物工程体验”的教育推广计划，目标是高中教师和女学生。该计划将通过在实验室环境中培训学生和教师，并允许教师将实验室模块带回课堂进行课程开发，将研究与教育相结合。这一方案的成功实施和发展将是增加妇女参与生物工程和相关科学领域的一种机制。