Contact Us

What is JoVE Visualize?

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer

Affiliations
  • 1Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 2Department of Thyroid Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 3Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 4Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 5Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 6Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 7Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. liuyih3@mail2.sysu.edu.cn.
  • 8Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. xiaohp@mail.sysu.edu.cn.

|

July 19, 2024

Abstract

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP’s function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.

Related Concept Videos

JoVE Research Video for Synthesis and Functions of Calcitonin 00:51

1.0K

Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital…

JoVE Research Video for Hormones and Bone Tissue 01:17

2.3K

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte…

JoVE Research Video for The Parathyroid Glands 00:59

1.4K

The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by…

JoVE Research Video for The Tumor Microenvironment 02:17

5.9K

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue…

JoVE Research Video for mTOR Signaling and Cancer Progression 03:03

3.5K

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the…

JoVE Research Video for Skeleton and Calcium Homeostasis 01:21

3.9K

Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.<br…