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

该PESO奖由马萨诸塞大学阿默斯特分校材料研究部的生物材料项目授予，由生物技术、生化、生物质工程项目（ENG/CBET）共同资助；材料与表面工程专业（ENG/CMMI）；以及国家癌症研究所物理科学肿瘤学办公室（OPSO）。转移是乳腺癌患者死亡的主要原因。乳腺癌远处肿瘤生长最常见的组织部位包括脑、肺、肝和骨。鉴于这些远端组织部位生物物理特性的明显多样性，本研究假设这些组织的物理和化学特性调节癌细胞的迁移和增殖能力，这是转移灶形成的两个关键步骤。该提案的目标包括：1)开发3D生物材料，可以通过设计来捕获这些组织部位（脑，肺和骨）的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；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以及癌细胞在这些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，系统地研究细胞外基质如何影响乳腺癌转移，并获得生物物理组织特性如何影响癌症转移生物学的基础知识。作为拓展活动的一部分，该项目计划与校园多元化项目合作，开展以女高中生和女教师为对象的暑期研究项目。项目负责人还建议制定计划，以评估教育和外展计划的成功，以及如何改进这些计划。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。阻碍进展的障碍之一是，绝大多数乳腺癌研究都是在塑料或玻璃表面培养细胞进行的，这些细胞是平坦的，非常坚硬，与复杂的、三维的、相对柔软的人体组织完全不同。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。有了这个奖项，在类组织环境中的3D结构将准备好使乳腺癌细胞认为它们是在真正的肿瘤组织中，或乳腺癌细胞最常转移到的组织，如骨、肺和脑。利用这些新颖的类组织系统，该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，癌症扩散到某些器官的倾向是因人而异的。出于这个原因，该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针对患者的。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，并且通过使用更像人体组织的材料，可能会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，这位研究者正在与校园多样性项目办公室合作，以高中教师和女学生为目标，开展一个名为“细胞工程：年轻女性的生物工程体验”的教育推广项目。该计划将通过在实验室环境中培训学生和教师来整合研究和教育，并允许教师将实验室模块带回课堂进行课程开发。该计划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。

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.