A Metastasis 'Magnet' for Early Cancer Diagnosis

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Attraction is commonplace: we are attracted to a significant other, certain metals are attracted to magnets, and moths are attracted to flames. In some instances, attraction is not preferred, especially in the case of cancer. Primary tumors initially form in a host organ, and cancerous cells are eventually attracted to other organs in the body, forming secondary tumors known as metastases. This characteristic of cancer is the most devastating, and is largely the reason why cancer is incurable. However, current research suggests that a cancer cell’s attraction to a specific organ can be used to detect and diagnose metastasis at an early stage in the hopes of combating the devastating disease, before it’s too late.

Over 1.6 million individuals are diagnosed with cancer each year in the U.S., according to the American Cancer Society. Currently, metastasis marks the stage of cancer progression when the disease is deemed to be incurable. The five-year survival rates of cancer patients drop precipitously when the primary tumor spreads cancer cells to various target organs to form metastatic tumors. This sharp decrease indicates there is an urgent need to develop new technologies to diagnose metastases before they grow and spread throughout the body.

The primary reason for the dismal survival rates is because there is currently no effective method to diagnose metastasis at an early stage. Virtually all types of cancers are able to metastasize. For instance, breast cancer cells can spread to the brain and bones, and colorectal cancer cells can spread to the lungs and liver. Unfortunately, these individual cancer cells remain undetectable until they have colonized and formed a new tumor mass at an organ.

Tests for metastasis depend on the location of the primary tumor, and largely depend on inadequate methods. An oncologist is able to diagnose a metastatic tumor using imaging techniques (most commonly CT scans), but only after the metastasis has grown to a visible mass. By then, the disease has progressed to a stage that is extremely difficult to treat. Standard treatments involve aggressive chemotherapy and surgical intervention and are not usually curative. Early diagnosis of metastatic cancer would significantly improve the survival rate of the patient.

Scientists have long been searching for ways to detect metastasis early. As far back as 1889, Dr. Stephen Paget developed the “seed and soil” hypothesis, claiming that cancer metastasis is “pre-determined,” and that cancer cells preferentially metastasize to specific organs. Similar to a plant, the cancer cell “seed” tends to flourish in a specific environment, or “soil.” Most cancers are attracted to specific organs, since they provide the necessary environment for cancer cells to grow.

The theory that a cancer cell is attracted to a specific microenvironment implies that an environment can be engineered to mimic the environment of an organ­. With this concept in mind, imagine if cancerous cells could be lured away from an actual organ to an implantable device that was engineered to mimic that organ and detect the cells’ arrival? Scientists at Northwestern University are making this a reality.

Professor Lonnie Shea and his team are developing a biomaterial implant for early metastasis detection. Biomaterials are materials that are not rejected by the body upon implantation. Common biomaterials include metals and ceramics used for joint and hip replacements, or soft hydrogels used for contact lenses. Biomaterials have also been utilized in the tissue-engineering field to replace diseased tissues and stimulate new tissue growth.

In the Shea Lab, the biomaterial implant, known as a scaffold, is used in projects involving tissue regeneration and cell transplantation. A scaffold is a porous biomaterial, similar in structure to a sponge. Cells are retained in the pores of the scaffold, which makes the material ideal for the recruitment of colonizing cancer cells. The scaffold is made from poly(lactide-co-glycolide) (PLG), a polymer often used to make biocompatible sutures.

In a paradigm shift, the lab is now using the PLG scaffolds to attract metastatic cancer cells, much like a magnet. After implantation, blood vessels grow near the scaffold, which provide passages for cancer cells to arrive to the scaffold. The scaffold exploits the ability of metastatic cells to travel throughout the blood vessels, and acts like a magnet to attract cancer cells to the scaffold before they are able to reach other organs. The scaffold allows doctors to identify the presence of metastases early, before secondary tumors have formed and the cancer has become mostly untreatable.

A PLG scaffold, designed to mimic the environment of an organ, "lures" cancer cells away from the organs they would normally be attracted to.A PLG scaffold, designed to mimic the environment of an organ, "lures" cancer cells away from the organs they would normally be attracted to, allowing doctors to detect metastasis early.

While the method has not been used in a human yet, the scaffolds have been implanted in tumor-bearing mice, and have shown extremely promising results in attracting cancer cells. The translation of this technology to a clinical setting would be relatively simple. When a patient presents with a primary tumor, the oncologist would remove the tumor using traditional methods (i.e. surgery, irradiation, chemotherapy). After removing the tumor, there may still be cancer cells circulating in the body. To capture these circulating cells, the surgeon would then implant the scaffold in a location under the skin far away from the primary tumor site. The scaffold would be engineered to mimic the environment of organs the cancer cells might normally like to populate. Ideally, the scaffold would attract cancer cells away from these organs, indicating to the doctor that metastasis is imminent.

To detect the cancer cells on the scaffold, innovative imaging techniques, also developed at Northwestern, are utilized. In collaboration with Professor Vadim Backman’s lab, an emerging imaging technique known as Inverse-scattering Optical Coherence Tomography (ISOCT) can be used to image the scaffold through the skin. Using a light scattering probe, small alterations in the scaffold architecture can be detected upon the arrival of cancer cells. ISOCT is able to distinguish the micro-structural changes of cancer cells compared to other cell types that may arrive to the scaffold.

This method may provide a simple means to image the scaffold during the patient’s course of treatment. When a patient goes to the clinic for a check-up after the primary tumor resection, the scaffold would be imaged to track the course of the disease and detect metastasis at an early stage. Although this imaging modality remains experimental, ISOCT provides promise for detecting cancer cells on the scaffold non-invasively. This technique would provide valuable time to treat the patient accordingly if metastatic cells are detected – thus helping to save the patient’s life.

At times, the most devastating characteristic of a disease can be a potentially innovative target for therapeutic intervention. A cancer cell’s attraction to an organ can be life threatening, but tricking the cell to be attracted to the scaffold could be life saving. Imagine a world where a metastatic cancer diagnosis is no longer a death sentence. With increased knowledge of how metastasis works, the development of new technologies for early detection could make metastasis treatable for the first time. Ultimately, this advancement would represent another significant triumph in the war against cancer.

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