Aging breast tissue could set the stage for invasive breast cancer


Date:
October 18, 2021
Source:
University of Notre Dame
Summary:
A new study examines how the extracellular matrix (ECM) -- an
underlying network of molecules and proteins that provide the
structure for tissue growth -- can trigger invasive cancer-related
genes.



FULL STORY ==========================================================================
The American Cancer Society estimates that 284,200 women will be newly diagnosed with breast cancer in 2021, and 43,600 will die of the disease
-- the second highest cause of cancer death in women.


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A woman's risk of being diagnosed with breast cancer increases with age,
but while scientists have long studied cellular changes that take place in
the body over time, a new study led by researchers at the University of
Notre Dame examines how the extracellular matrix (ECM) -- an underlying
network of molecules and proteins that provide the structure for tissue
growth -- can trigger invasive cancer-related genes.

"This is the first time we've been able to show direct evidence that
the aging ECM itself is changing the phenotype of normal epithelial
cells," said Pinar Zorlutuna, the Sheehan Family Collegiate Professor
of Engineering at Notre Dame and principal investigator of the study,
published in Advanced Science.

"Clinical data shows that aging is a big risk factor for breast cancer,
and we wanted to investigate why that is. Cellular aging has been
explored, but what we didn't know was what effect aging had on the extracellular matrix." Zorlutuna and her team studied the ECM tissue
in healthy younger and older mouse models, seeding the matrixes with
normal mammary epithelial cells - - cells that form a thin layer of
tissue around the breast -- and cancerous cells.

The research team found changes in the biochemical composition, structure
and stiffness of the aged ECM. As the tissue ages, protein levels and
collagen production decrease, and collagen fibers become thinner but
curlier and form a denser "mesh." Lack of collagen production can leave
the integrity of the ECM vulnerable to invasive tumor cells, while thinner
and curlier fibers may contribute to the metastasis of cancer cells.

"The normal epithelial cells in the aged matrix started to express more invasiveness-related genes associated with breast cancer," Zorlutuna
said. "And we identified the gene critical to this transition called
lysyl oxidase (LOX)." Normal epithelial cells grown on aged ECMs
showed an elevated expression of LOX, preventing the formation of
healthy cellular structures. In the models containing cancer cells,
those cells became more motile and invasive. When LOX was inhibited,
the study showed the original phenotype of the cells could be rescued -- meaning the epithelial cells returned to normal and were less motile as
they were in young and healthy ECM models.

The results could help scientists gain a better understanding of cell
migration and invasion in aged tissues and inform new methods for
prognosis, diagnosis and prevention of breast cancer. Zorlutuna said
she and her team will continue to study the ECM as it relates to cancer initiation and progression.

Zorlutuna is an affiliate member of Notre Dame's Harper Cancer Research Institute, Institute for Precision Health and Nanoscience and Technology.

Co-authors of the study include Gokhan Bahcecioglu, Ian Guldner, Erin
Howe, M.

Sharon Stack, Xiaoshan Yue and Siyuan Zhang at Notre Dame and Harikrishna Nakshatri at Indiana University.

The National Institutes of Health, the Walther Cancer Foundation and
Notre Dame's Harper Cancer Research Institute funded the study.

========================================================================== Story Source: Materials provided by University_of_Notre_Dame. Original
written by Jessica Sieff. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Gokhan Bahcecioglu, Xiaoshan Yue, Erin Howe, Ian Guldner, M. Sharon
Stack, Harikrishna Nakshatri, Siyuan Zhang, Pinar Zorlutuna. Aged
Breast Extracellular Matrix Drives Mammary Epithelial Cells to an
Invasive and Cancer‐Like Phenotype. Advanced Science, 2021;
2100128 DOI: 10.1002/advs.202100128 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211018105920.htm

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