Tumor Matrix Profile May Indicate Poor Outcome in Squamous Cell Carcinoma

Researchers in Australia have characterized the molecular profiles of tissue surrounding squamous cell carcinoma—a common type of lung cancer—and say the findings could identify which patients are likely to develop aggressive tumors.

Squamous cell carcinoma is the second most prevalent type of lung cancer. Less than one in five patients survive five years past diagnosis because of the cancer’s high rate of recurrence and chemotherapy resistance. 

Researchers at the Garvan Institute of Medical Research sought to uncover how the environment that surrounds these tumors—known as the tumor matrix—is altered to promote tumor growth.

“Tumors are an ecosystem, made up of cancer cells held together by the matrix—it is this matrix that we think is supporting cancer cells to keep growing and spreading, contributing to the poor outcome for some patients,” says Dr. Amelia Parker, first author of the study. “But we didn’t really have an understanding of what the matrix looks like or why it makes lung cancer resistant to treatment. If we can understand that part of the tumor, we can reveal more effective ways to treat patients by targeting the way the matrix is making the cancer more aggressive.”

The Garavan team, led by Associate Professor Thomas Cox, comprehensively studied the molecular and protein composition of the matrix around squamous cell carcinoma lung tumors, taken from patient tissue samples. They identified two tumor matrix profiles, one in which patient prognosis was good, and the other where patients did poorly. These matrix profiles appear to be established early in the initiation of the tumor and persist as the tumor grows, controlling how the tumor will respond to chemotherapy treatment.

The tumor matrix in patients who fared worse had more collagen proteins and more fibrosis—stiffening of the tumor structure—suggesting that the tumor matrix remodels to protect itself against treatment.

The team also found that, while adenocarcinomas and squamous cell carcinomas appear similar in the clinic, they are quite different in their matrix composition. These differences have the potential to be leveraged by existing therapies developed to treat other diseases.

“These two tumors look very similar under the microscope, and are typically treated the same way, but are very different on a molecular level,” says Cox, head of the Matrix and Metastasis lab at Garvan. “This sheds light on why some patients progress well and others don’t, and how we might be able to stratify patients to provide more personalized treatment.”

The next step is to engage with clinical partners to move toward a clinical trial for repurposing therapies that may prevent this matrix remodeling in lung cancer patients, and improve response to therapy.

The findings were published in BMC Genome Medicine.