USA Study Reveals Pathway in Cancer Metastasis – University of South Alabama

University of South Alabama Research on Cancer and Nerve Cell Interactions

Introduction

Research at the University of South Alabama has uncovered critical insights into how cancer cells exploit their microenvironment, particularly nerve cells, to promote growth and metastasis. Published in Nature, these findings contribute to the understanding of cancer complexity and support the development of novel therapies aligned with Sustainable Development Goal (SDG) 3: Good Health and Well-being.

Research Leadership and Collaboration

• Led by Dr. Simon Grelet, Assistant Professor of Biochemistry and Molecular Biology at the Frederick P. Whiddon College of Medicine.
• Collaboration with Dr. Gustavo Ayala’s group at McGovern Medical School/UTHealth and Dr. Mike Lin at Whiddon College of Medicine.
• Supported by National Institutes of Health, Breast Cancer Research Foundation of Alabama, and other institutional funds.

Key Findings and Methodologies

Nerve Cells Drive Cancer Progression

1. Discovery that nerve cells actively promote cancer progression by transferring mitochondria to tumor cells, enhancing their survival under metastatic stress.
2. Use of innovative breast cancer models to study nerve-cancer cell interactions.
3. Application of botulinum neurotoxin type A (Botox) to block nerve-tumor communication, resulting in slower tumor growth and reduced aggressiveness.

Metabolic Interactions and Mitochondria Transfer

• Identification of intimate physical contacts between neurons and cancer cells via high-resolution microscopy.
• Recognition of neuronal metabolic efficiency driven by mitochondria, which cancer cells hijack to boost energy production.
• Development of flow cytometry and custom software tools to quantify mitochondrial DNA transfer, showing a 35% reduction when nerve signaling is blocked.

Innovative Tools: MitoTRACER

The research team developed MitoTRACER, a synthetic biology tool that permanently labels cancer cells receiving mitochondria from neurons by triggering a color change. This advancement facilitates the study of intercellular mitochondrial transfer and is currently under patent application.

Implications for Cancer Metastasis and Therapeutic Strategies

Metastasis and Metabolic Plasticity

1. Cancer cells acquiring neuronal mitochondria show increased presence in brain and lung metastases, indicating enhanced adaptability to metastatic stress.
2. Findings suggest targeting metabolic plasticity of cancer cells rather than solely focusing on motility may improve therapeutic outcomes.

Alignment with Sustainable Development Goals (SDGs)

• SDG 3: Good Health and Well-being – Advancing cancer research to improve treatment and patient outcomes.
• SDG 9: Industry, Innovation, and Infrastructure – Development of novel research tools like MitoTRACER fosters innovation in biomedical sciences.
• SDG 17: Partnerships for the Goals – Collaborative efforts across institutions exemplify effective partnerships to address global health challenges.

Recognition and Future Directions

• Dr. Christopher Davies, Associate Dean for Research, highlighted the publication in Nature as a significant scientific achievement.
• Dr. John V. Marymont, Dean of Whiddon College of Medicine, emphasized the research’s impact on understanding metastasis and future healthcare.
• Ongoing research aims to further elucidate nerve-cancer interactions and develop targeted therapies to prevent metastasis.

1. Sustainable Development Goals (SDGs) Addressed or Connected

1. SDG 3: Good Health and Well-being
   • The article focuses on cancer research, specifically breast cancer progression and metastasis, which directly relates to ensuring healthy lives and promoting well-being.
2. SDG 9: Industry, Innovation and Infrastructure
   • The development of innovative models, such as the nerve-cancer co-culture model and the MitoTRACER genetic tool, reflects advances in scientific research infrastructure and innovation.
3. SDG 17: Partnerships for the Goals
   • The research involved collaboration between multiple institutions and experts, highlighting the importance of partnerships in advancing scientific knowledge.

2. Specific Targets Under the Identified SDGs

1. SDG 3: Good Health and Well-being
   • Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.
   • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries.
2. SDG 9: Industry, Innovation and Infrastructure
   • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors, including encouraging innovation and increasing the number of research and development workers.
3. SDG 17: Partnerships for the Goals
   • Target 17.16: Enhance the global partnership for sustainable development, complemented by multi-stakeholder partnerships that mobilize and share knowledge, expertise, technology and financial resources.

3. Indicators Mentioned or Implied to Measure Progress

1. SDG 3 Indicators
   • Indicator related to cancer mortality and morbidity rates, implied by the focus on understanding cancer progression and metastasis.
   • Clinical correlation of nerve density in tumors with patient prognosis, which could be used as a biomarker indicator.
2. SDG 9 Indicators
   • Number of scientific publications and patents filed, as evidenced by the publication in Nature and the pending patent for MitoTRACER.
   • Development and application of innovative research tools and models (e.g., nerve-cancer co-culture model, MitoTRACER genetic tool).
3. SDG 17 Indicators
   • Number and quality of collaborative research projects involving multiple institutions and disciplines.
   • Funding amounts and sources supporting collaborative research initiatives.

4. Table of SDGs, Targets, and Indicators

Source: southalabama.edu