OBESITY is a risk factor for many cancer types, including endometrial, liver, ovarian, kidney, colorectal an​d postmenopausal breast cancers. What’s less clear i​s how fat contributes to cancer risk and progression.

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Cornelia Ulrich Photo courtesy of Cornelia Ulrich

T​o​ better understand this role, cancer epidemiologist Cornelia Ulrich of Huntsman Cancer Institute in Salt Lake City and colleagues recently analyzed studies that explore how fat cells, also called adipose tissue, send signals to cancer cells. “We have evidence now for a bidirectional interaction that goes back and forth between the adipose cells and the tumor cells,” Ulrich says.

The research, published in the September 2017 Cancer Prevention Research, suggests that different types of adipose tissue may play different roles in cancer development, growth and metastasis, depending on its location and proximity to the tumor tissue. For example, cells in the breast are made up of fat that secretes different signals than fat packed tightly around abdominal organs. The latter type of fat, known as visceral adipose tissue, is considered more metabolically active than other types of fat, but scientists have yet to understand the role these fat cells play in cancer development and spread.

Ulrich spoke with Cancer Today about the obesity-cancer link and what this could mean for patients.

CT: Do fat cells appear to have a role in cancer development?
ULRICH: What we have learned over the past years is that adipose tissue secretes substances that can be relevant for the growth of tumors.

CT: How could fat fuel cancer cells?
ULRICH: There are what we call paracrine and endocrine relationships. Paracrine is the relationship where cells secrete substances that then can interact with tissues in their direct proximity. Endocrine means that those substances from the fat cells can go into the bloodstream and then come back to all cells in the body, including the tumor cells. The endocrine relationship is well-established. If you have a higher body mass index, then you’re going to have higher markers of inflammation in your blood, such as C-reactive protein. We know that inflammation is a hallmark of cancer. We are now exploring the role of the paracrine relationship, which is potentially very important as well. One key question that’s just beginning to get investigated is this: Is there direct crosstalk between fat cells and cancer cells for tumors that can be right next to adipose tissue, embedded in adipose tissue or where adipose cells are part of the tumor? That is a very recent concept that we’re just beginning to understand.

CT: What role does visceral fat play?
ULRICH: Visceral fat that’s in a certain area in the abdomen is metabolically much more active. It’s like a little powerhouse of fat and is most closely linked to diabetes or other biomarkers that are related to diabetes and metabolic syndrome. The fat that’s sitting under the skin, the subcutaneous fat, doesn’t seem to be as active. The visceral fat seems to be more dangerous in the sense that it secretes more substances that can be tumor-promoting, but again, we do need more studies. We know the visceral fat is more aligned with an inflammatory status of the body.

CT: Can you tell if a person has more visceral fat by looking at a person?
ULRICH: Unfortunately you cannot. You have to do imaging. Two people may appear chubby on the outside and one person will have a lot of visceral fat and the other person will not. You can look at it on a CT scan or an MRI—and cancer patients often get CT scans as part of their clinical follow-up.

CT: Is there another way to analyze this?
ULRICH: Yes, inflammation, measuring markers such as C-reactive protein, is one way. Body mass index is the most important predictor of C-reactive protein in the body. It appears, from a number of studies, that it’s the visceral fat, or intra-abdominal fat, that is associated with increased C-reactive protein levels.

CT: What do you think cancer patients and survivors should know about fat?
ULRICH: We do know from our studies in healthy people that if you do strength training or core training, you can reduce your intra-abdominal fat and that generally a healthy body weight is associated with a reduced risk of cancer recurrence. Exercise, and in particular strength training, has many added benefits for cancer patients. It helps reduce fatigue. It helps them to remain very mobile and get back to their normal lives more quickly.

CT: Can it be difficult for cancer survivors and patients to exercise?
ULRICH: It’s incredibly hard sometimes when you’re already feeling fatigued to go out and exercise. But if you just take small steps, you may feel better and can potentially reduce that influence of fat in your body. We’ve done some studies in healthy overweight people who exercised for a year. They didn’t lose much weight, but they changed their internal composition. Their intra-abdominal fat was lower, and they ended up having a substantial reduction of their C-reactive protein levels in the blood. Studies show exercise can have an impact on fat composition, which may be encouraging for people.