October is Breast Cancer Awareness Month, and fittingly, University of New Mexico Comprehensive Cancer Center biologist Curt Hines, PhD, has published a pair of papers that comprehensively describe the twelve major types of cells in the human breast.
“We are trying to understand all the different cell types that are collaborating and coordinating to make a tissue function,” he says, “and how these processes can go awry in a tumor.”
Over the past several decades, breast cancer has become a leading cause of cancer deaths among women, second only to lung cancer. Of all cancer types diagnosed in women each year, a third will be breast cancer—and there is a 1 in 8 chance that a woman will develop breast cancer over her lifetime.
According to the National Cancer Institute, between 75% and 80% of breast cancer cases have features of luminal epithelial cells, which are a special cell type that forms the milk ducts of the breast. Cancers of this type are called ductal adenocarcinomas.
You need to know all the cell types in a tissue. Tumors are diseases of the tissue. You really need to understand all the players.
Organs and tissues comprise different types of cells that work together to form a functional unit. This normal balance of cell types is disrupted in tumors. These other non-cancerous cells influence how tumors behave.
“You need to know all the cell types in a tissue,” Hines says. “Tumors are diseases of the tissue. You really need to understand all the players.”
For the past 10 years, Hines’ laboratory has been compiling information about the types of cells in human breast tissue. Recently, he and his team published a pair of papers about their work.
The first paper, published this month, describes the process they used to identify, purify, and grow every major cell type in the human breast. The second paper, in press at PLOS Biology, describes in great detail each of the twelve major types of cells in a human breast.
Hines used non-diseased breast tissue that was discarded in breast reduction surgeries. He then used two different technologies — flow cytometry and RNA sequencing — to find, select and describe the cell types in those tissue samples.
Hines began his work using tissue staining and flow cytometry, which can analyze hundreds of thousands of cells by their specific traits, utilizing the UNM Comprehensive Cancer Center’s Flow Cytometry Shared Resource. After unlocking the combination of specific antibodies required to detect all cell types, he and his team used flow sorting to isolate the different breast cell types. They then used RNA-sequencing to analyze the RNA transcripts made by each cell type.
RNA sequencing determines the sequences of all the different ribonucleic acid (RNA) transcripts in a cell. RNA transcripts are molecules that are copied from the DNA genome. These transcripts carry the code for the proteins that accomplish the cell’s processes; they define the nature and properties of that cell type.
“Every cell in an individual has the same DNA,” Hines says, “but they don’t have the same RNA. And it’s the RNA that tells the cell what to do, what their function is.”
Flow cytometry enabled Hines to identify the twelve different cell types composing the breast. He and his team purified each cell type to study them in greater detail. Guided by the differences in the RNA transcripts, they closely examined the biological nature of each cell type.
The resulting information was immense, as each cell type was found to express more than 20,000 individual genes. Among their findings, Hines and his team discovered a rare epithelial cell type which appeared to have stem cell properties. Stem cells have the ability to mature into an array of different cell types and serve as part of the body’s repair systems.
To further explore how the cells function, it was necessary to keep the cells alive in the laboratory—by growing them in plastic tissue dishes with cell medium—a mixture of sugars, amino acids, vitamins, and serum.
Hines and his team created cell models from nearly every cell type, expanding on the two to three that are commonly used in breast research. Their cell models are grown in the laboratory, and these cells retain the defining characteristics that they exhibit in the body. These cell models will enable scientists to study the behavior of the different cell types and explore how each cell type may contribute to the malignant process of tumor formation.
The cell types and their descriptions are summarized in the published papers, and full data about each type is available online.
“We were really trying to get to the essence of each cell type,” Hines says. “There’s so much information.”
Hines says that the reference can help biologists who want to understand what all the different types of cells in a human breast do and how a disturbance in the balance of these cells can lead to cancer.
Hines and his team are now studying pericytes and how these cells may influence the growth of breast tumors. They are also using the breast cell reference to study how breast cells influence their microenvironment and how their microenvironment influences them. The single-cell RNA sequencing capabilities at UNM Cancer Center’s Analytical and Translational Genomics shared resource have permitted Dr. Hines to explore the heterogeneity within the breast’s pericyte population. Their next grant proposal aims to elucidate the pericyte’s contributions to breast malignancies.
“We know that disturbing the microenvironment can propel tumor growth,” Hines says, but he also marvels that many cancer cells do not turn into tumors. “It's amazing that our tissues work in the way that they do.”
About Curt Hines, PhD
Curt Hines, PhD, is an associate professor at The University of New Mexico School of Medicine Department of Biochemistry and Molecular Biology. He is the Faculty Director of the UNM Comprehensive Cancer Center Flow Cytometry Shared Resource and Director of the Undergraduate Honors Research Program for Biochemistry majors.
Paper References
“Comprehensive identification, isolation, and culture of human breast cell types” was published online on August 7, 2024, in Journal of Biological Chemistry (https://www.sciencedirect.com/journal/journal-of-biological-chemistry). Authors are Kate Thi, Katelyn Del Toro, Yamhilette Licon-Munoz, Rosalyn W. Sayaman, and William C. Hines.
“Transcriptomic analysis of the twelve major human breast cell types reveals mechanisms of cell and tissue function” In Press, PLOS Biology (available on November 5, at: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002820). Authors are Katelyn Del Toro, Rosalyn W. Sayaman, Kate Thi, Yamhilette Licon-Munoz, and William C. Hines.
Online Tools:
Breast Cell Gene Atlas – Hines Lab (breastcancerlab.com)
UNM Comprehensive Cancer Center
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius.
Its more than 136 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 600 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provide treatment to 65% of New Mexico’s cancer patients from all across the state and partner with community health systems statewide to provide cancer care closer to home. They treated almost 15,000 patients in more than 100,000 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital.
A total of nearly 1,855 patients participated in cancer clinical trials testing new cancer treatments that include tests of novel cancer prevention strategies and cancer genome sequencing.
The more than 123 cancer research scientists affiliated with the UNMCCC were awarded $38.2 million in federal and private grants and contracts for cancer research projects. Since 2015, they have published nearly 1000 manuscripts, and promoting economic development, they filed 136 new patents and launched 10 new biotechnology start-up companies.
Finally, the physicians, scientists and staff have provided education and training experiences to more than 500 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery.