Chemical Engineering Ph.D. student Ryan Carpenter has received an AACR-Bristol-Myers Squibb Scholar-in-Training Award in the amount of $1,500 from the American Association for Cancer Research (AACR), based on the quality of his award application and abstract entitled “Implantable tumor attracting niche models to study disseminated tumor cell biology.”
Carpenter received his award at the AARC Annual Convention in Atlanta on March 30, when a Scholar-in-Training Awards reception was held at the Hyatt Regency Atlanta. Carpenter is the Ph.D. student of Chemical Engineering Professor Junwoo Lee of the ChE department.
Scholar-in-Training Awards are competitive and are presented to those with high-quality abstracts and applications from a large candidate pool.
According to Carpenter’s abstract, metastasis is the leading cause of death in cancer but remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse.
Carpenter says that mouse models have been widely used to study metastasis, however they are limited for prolonged investigation of the post-dissemination phase of cancer cell biology due to the rapid onset of actively growing primary and secondary tumors. This limitation has left a critical gap in understanding the long-term, bi-directional crosstalk between DTCs and their local microenvironment due to the relatively short experimental timeframe.
As Carpenter’s abstract says, “Here we introduce an implantable tissue engineered metastasis model that can overcome the fundamental restrictions of existing mouse models and substantiate the role of the tumor microenvironment in the reactivation of dormant DTCs with molecular and cellular detail.”
The abstract goes on the explain that subcutaneous implantation of porous collagen-coated acrylamide scaffolds, fabricated as previously described, modulate the foreign body response to induce the formation of a robust vascularized tissue. During tissue formation and local inflammation, the scaffold generates a pre-metastatic niche, characterized by the recruitment of circulating tumor cells and, given time, the formation of overt metastases. However, mice became moribund before meaningful investigation of dormant tumor cell biology could occur due to increasing tumor burden.
“We addressed this limitation via intact transplantation of the DTC microenvironment to tumor-free mice,” as Carpenter writes. “Scaffolds have been maintained in secondary mice for up to 10 weeks. Compared to transplanted DTC-bearing lung tissue, scaffolds maintained an inactive phenotype for longer periods. At the end of this period, transplanted scaffolds captured three distinct DTC phenotypes: dormant, early colonization, and overt metastasis.”
Carpenter concludes that “Our results demonstrate the potential of a tissue engineering approach to generate pre-metastatic niches and investigate the transient activity of the DTC niche during tumor cell awakening and subsequent metastasis. We envision that implantable microenvironments will be an enabling tool to study DTC biology and aid in the development of anti-metastatic therapies.”
Funds have been graciously donated to the AACR to recognize outstanding young investigators for their meritorious work in cancer research and to support their attendance to the 2019 AACR Annual Meeting, which took place from March 29 to April 3, 2019, in Atlanta. The award funds were used to defray travel, subsistence, and registration expenses to attend the AACR Annual Meeting. (April 2019)