内分泌外分泌信号が肥満に関連した臓管内腺癌を誘発する

Katherine Minjee Chung¹, Jaffarguriqbal Singh², Lauren Lawres²

¹Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.

Cell

|April 19, 2020

まとめ

肥満は新しい変異ではなく,微小環境の変化によって臓がん (PDAC) の進行を促進します. 体重減少は,この効果を逆転させ,癌の発症における小島細胞のシグナリングを強調します.

科学分野:

腫瘍学
内分泌学
代謝疾患の研究

背景:

肥満は臓管腺がん (PDAC) の重要なリスク因子です.
肥満がPDACの進行に影響する正確なメカニズムとタイミングは不明である.

研究の目的:

肥満とPDACの早期進行との因果関係を解明する.
肥満がPDAC腫瘍形成に及ぼす影響を媒介する分子および微環境的要因を特定する.

主な方法:

初期のPDACの発達を研究するために本土のマウスモデルを使用した.
ヒトとマウスのサンプルを分子分析した.
肥満に関連するPDACにおける臓小島細胞の適応とペプチドホルモン発現の役割を調査した.

主要な成果:

早期PDAC腫瘍形成の促進における肥満の因果と逆転の役割が示された.
遺伝子や食事によって引き起こされる体重減少が癌の発症を効果的に阻害することを示しました
肥満における異常なベータ細胞発現 (Cck) が確認され,これはKras主導のPDACを促進する.
肥満に関連した微小環境の変化が PDACの進行を誘導する事が分かりました

結論:

肥満は局所的な腫瘍の微小環境の変化によってPDACの進行を著しく促進する.
肥満に起因するPDACにおいて異常な小島細胞シグナル伝達,特にCckは重要な役割を果たします.
インスリン以外の内分泌外分泌信号はPDACの発現に関与しており,潜在的な治療標的を提供している.

キーワード:

ベータ細胞コレシストキニン遺伝子組み換えマウスモデルレプチン肥満臓がん臓の小島腫瘍の微小環境

さらに関連する動画

10:17

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes

Published on: April 26, 2019

7.3K

09:48

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

Published on: February 17, 2023

3.3K

関連する概念動画

01:45

Endocrine Signaling

67.4K

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.

67.4K

01:01

Autocrine Signaling

51.7K

Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...

51.7K

01:28

Insulin: The Receptor and Signaling Pathways

2.4K

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...

2.4K

01:24

Obesity

1.1K

The Body Mass Index (BMI) is a numerical value derived from a person's weight and height, used to categorize individuals into weight ranges. It is calculated using the formula: weight in kilograms divided by height in meters squared. Obesity is a health condition characterized by excessive accumulation of adipose tissue that poses health risks, often diagnosed with a BMI ≥ 30. This excess fat storage occurs when surplus dietary calories are converted into triglycerides and stored in...

1.1K

01:36

Carbohydrate Metabolism

13.5K

Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...

13.5K

01:08

Chemical Signaling in the Endocrine System

5.9K

A signaling cascade is a series of events that facilitates the transmission of information within or between cells, culminating in a targeted response in the recipient cell. As chemical messengers, hormones are pivotal in initiating and modulating these intricate signaling cascades based on their solubility.
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...