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Two Cells

The Tiny World around a Cancer Cell

For a long time, scientists focused on tumors as isolated growths – a group of cells gone bad. Yet like anything else, cancer cells do not live in a void; they continuously interact with their environment. In recent years, AICR scientists have gained a new understanding of how a cell’s surroundings can drive or stifle cancer growth, and how dietary substances may alter the microenvironment to suppress cancer.

“A tumor isn’t just cancer cells, it is a set of cancer cells interacting with the host,” said Steven K. Clinton, M.D., Ph.D. a Professor at the College of Medicine at Ohio State University and a speaker at AICR’s upcoming annual research conference in November. “It does this by impacting various aspects of the microenvironment, some of which come from the host and some from the tumor.”

The tumor microenvironment consists of different types of healthy cells and a surrounding matrix, a gel-like substance that binds cells together. There are immune cells, proteins that produce growth factors, and epithelial cells, which line our organs. There are cells that provide structure and play a role in wound healing. There are also cells that make up and line blood vessels, which are one of the key requirements for tumor growth and a research focus of Dr. Clinton’s.

Stopping the Food Supply

“In order for cancer to grow it needs nutrients, oxygen, and to get rid of metabolic waste. It needs to create in the microenvironment a vascular system to achieve that,” said Dr. Clinton. “The interesting thing is we know from diet and nutrition studies with lab animals is that we can change tumor vascularity… either directly or indirectly.”

While a tumor is still small it draws from existing blood vessels. But in order to develop and spread, the tumor needs to form a network of new vessels by a process called angiogenesis. In angiogenesis, tumor cells send out a signal that orchestrates the formation of new blood vessels punching their way through the matrix and feeding the tumor. Block or prevent the signal and angiogenesis stops.

In a series of studies, Dr. Clinton and his colleagues have shown that genistein, a phytochemical in soy, reduced blood vessel density and prostate tumor growth in mice. A cell study, supported by AICR, revealed several possible ways that genistein may disrupt the signaling pathways related to prostate cancer angiogenesis. Among the mechanisms, the study found that genistein reduced the signals cancer cells produce.

The Seed and Soil
The idea of the microenvironment affecting cancer growth was first proposed with the “seed and soil” hypothesis, back in the late nineteenth century. An English scientist was trying to understand why certain cancers tended to spread to specific organs. For examples, breast tumors generally spread to the lung. It appeared, he hypothesized, that only certain organs provided the “fertile ground” needed for growth.

A Healthy, Cancer-Free Environment

Whether cancer starts and takes root in the first place depends on a fertile microenvironment. With the link between excess body fat and increased colon cancer risk now clear, scientists at Michigan State University began investigating how a fat hormone may alter the microenvironment and promote cancer.

In recent lab studies, the scientists demonstrated that precancerous colon cells responded differently to leptin than normal cells. Leptin is a hormone that plays a key role in regulating fat metabolism. “The normal cells didn’t care if they saw the leptin, but the precancerous cells proliferated,” said Jenifer Fenton, Assistant Professor in Food Science and Human Nutrition and co-author of the study.

When bathed in elevated levels of leptin, the precancerous cells also started signaling to other cells to help them grow. The normal cells did not.

“Why is it that in some people the polyp stays benign and in others it turns into a tumor?” says Dr. Fenton. “It needs these promoters in the microenvironment for cell growth. Once we know the mechanisms, she said, the hope is to find a dietary compound that affects it and alters the microenvironment groundwork in the earliest stages.

— Excerpted from an article in ScienceNow.

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