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Characterizing breast cancer invasion and proliferation when co-aggregated with adipocytes in multicellular spheroids created with a custom bioreactor to augment cell-cell connectivity.

Award Number: SC3GM144192
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Breast cancer is the most common form of cancer in women and is considered a modern-day epidemic, especially because of the high degree of heterogeneity. Multiple studies have shown that the tumor microenvironment contributes to cancer growth and chemoresistance. Cancer-adipocyte interactions have gained increased attention as the crosstalk between them has been shown to promote tumor proliferation and increased cancer migration. However, the physiological relevance of previous co-culture methods is questionable. Several past studies did not use human cells, or differentiate between white and brown adipocytes, which have different phenotypes. In this proposal we will analyze tumor invasiveness of human triple negative and luminal A breast cancer cells when co-cultured with human brown and white adipocytes. To do this, we propose to use a 3D multicellular tumor spheroid system. Tumor spheroids provide a physiological relevant environment to study cancer biology and drug discovery. Compared to 2D paradigms, research shows 3D models better recapitulate chemoresistance and tumor growth found in human in vivo tumors. In the lab, we have developed a bioreactor that uses surface vibrations to produce Faraday waves that aggregate cells inside a liquid chamber. Devices with similar technology have been used to assemble scaffold-free 3D cell constructs and spheroids in a rapid and scalable way, without the need for additional chemicals or intrusive procedures. In this grant, we also seek to determine if this technology generates multicellular spheroids with greater cell-cell adhesion, compared to standard self-assembly. To achieve the scientific and technological goals of this grant, two specific aims are proposed: The first aim will compare the viability and connectivity of multicellular spheroids formed with our surface vibration bioreactor versus standard self-assembly spheroids. The second aim will measure changes in tumor invasiveness and proliferation in tumor spheroids made with human cancer cells and human adipocytes. We will compare two different types of breast cancer cells: triple negative and luminal A and two different types of adipocytes: white and brown adipocytes. These combinations will allow us to investigate the interactions of different cancer phenotypes with specific adipocyte cell types. Overall, the proposed research will have a major scientific and technological impact by expanding our understanding of breast cancer-adipocyte interactions and testing a technology that could deliver multicellular spheroids with improved intracellular connectivity in a scalable manner. This will significantly impact the field of cancer biology and therapeutics, as cancer-adipocyte associations have been observed in a multitude of tumors, including prostate, ovarian, and pancreatic cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $111,750 )
2024	2024	CALIFORNIA STATE UNIVERSITY SAN MARCOS CORP	333 S TWIN OAKS VALLEY RD	SAN MARCOS	CA	92096	SAN DIEGO	USA	Biomedical Research and Research Training	001	3	5/3/2024	NON-COMPETING CONTINUATION	$0
2024	2024	CALIFORNIA STATE UNIVERSITY SAN MARCOS CORP	333 S TWIN OAKS VALLEY RD	SAN MARCOS	CA	92096	SAN DIEGO	USA	Biomedical Research and Research Training	000	3	5/1/2024	NON-COMPETING CONTINUATION	$111,750
														Subtotal = $111,750

Issue Date FY: 2023 ( Subtotal = $111,750 )
2023	2023	CALIFORNIA STATE UNIVERSITY SAN MARCOS CORP	333 S TWIN OAKS VALLEY RD	SAN MARCOS	CA	92096	SAN DIEGO	USA	Biomedical Research and Research Training	000	2	5/22/2023	NON-COMPETING CONTINUATION	$111,750
														Subtotal = $111,750

Issue Date FY: 2022 ( Subtotal = $111,750 )
2022	2022	CALIFORNIA STATE UNIVERSITY SAN MARCOS CORPORATION	333 S TWIN OAKS VALLEY RD	SAN MARCOS	CA	92096	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	5/31/2022	NEW	$111,750
														Subtotal = $111,750

Grand Total All Awards = $335,250

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Characterizing breast cancer invasion and proliferation when co-aggregated with adipocytes in multicellular spheroids created with a custom bioreactor to augment cell-cell connectivity.

Award Number: SC3GM144192

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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