Bussard Research

Contact

Name: Karen Bussard, MS, PhD
Position: Associate Professor

233 South 10th Street
Bluemle Life Sciences Building, Room 624A
Philadelphia, PA 19107

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Highlighted Publications

Bussard KM, Venzon DJ, Mastro AM. (2010). Osteoblasts are a major source of inflammatory cytokines in the tumor microenvironment of bone metastatic breast cancer. J Cell Biochem. 2010 Dec 1;111(5):1138-48.  (PDF)

This publication was the first to show that osteoblasts are major contributors to the bone metastatic process.  Here, we found that bone metastatic breast cancer cells co-opt osteoblasts to undergo an inflammatory stress response, and produce large amounts of a classic set of inflammatory cytokines (IL-6, IL-8/MIP-2, VEGF, MCP-1, and GRO-alpha/KC).  These inflammatory cytokines were found to facilitate breast cancer cell colonization and survival in the bone tumor microenvironment.

Bussard KM, Okita N, Sharkey N, Neuberger T, Webb A. Mastro AM. (2010). Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur, a target area for metastatic breast cancer cell colonization. Clin Exp Metastasis. 2010 May;27(5):331-40. (PDF)

This publication was the first to localize the inflammatory cytokines IL-6, MCP-1, and VEGF in bone compartments via immunohistochemistry.  Here, we illustrated that the inflammatory cytokines VEGF and MCP-1 are found specifically in the trabecular bone metaphyses, and not in cortical bone.  Trabecular bone is an area to which metastatic breast cancer cells specifically colonize.  Metastatic breast cancer cells, on the other hand, also produced VEGF, and its expression was associated with increased tumor growth in bone.  Furthermore, we found that IL-6 was specifically expressed throughout the bone marrow.  Thus, these data suggest that the bone-derived inflammatory cytokines IL-6, MCP-1, and VEGF aid in breast cancer cell trafficking to trabecular bone.  

Bussard KM, Gay CV, Mastro AM. (2008). The bone microenvironment in metastasis; what is special about bone? Cancer Metastasis Rev. 2008 Mar;27(1):41-55. (PDF)

This is a review of why the skeleton is a desirable place for many types of cancer metastases, including breast cancer.  The review includes in depth discussion of bone physiology and anatomy, and how this leads to breast cancer cell dissemination to bone.   The review additionally discusses the major cells of the bone, the osteoblasts and osteoclasts, and how their normal activities lead to the attraction of metastatic breast cancer cells, as well as their maintenance and survival.

Bussard KM, Boulanger CA, Booth BW, Bruno RD, Smith GH (2010). Reprogramming human cancer cells in the mouse mammary gland. Cancer Res. 2010 Aug 1;70(15):6336-43. (PDF)

This publication was the first to demonstrate that the regenerating mammary gland has the capability to interact with and direct (reprogram) embryonal carcinoma cells to differentiate into cells that exhibit diverse ‘normal’ mammary cell phenotypes.  This publication was also the first to show that human cells are capable of recognizing signals from the mouse mammary gland in-vivo.  Here, we showed that, when mixed with ‘normal’ mammary epithelial cells and implanted into epithelium-divested mammary glands, human embryonal carcinoma cells proliferated in-vivo, expressed mammary epithelial cell markers cytokeratin 5 and 14, and produced the mouse milk proteins alpha-lactalbumin and lysozyme in a chimeric mammary outgrowth.

Bussard KM, Smith GH. (2012). Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo. PLoS One. 2012;7(11).   (PDF)

This publication was the first to show that human metastatic breast cancer cells are capable of being redirected by the regenerating mammary fat pad into cells that express mammary epithelial cell markers and milk proteins.  Additionally, human metastatic breast cancer cells were found adjacent to both mammary myoepithelial cells and basal cells in the mammary gland microenvironment, and contributed to the formation of a differentiated mammary gland, notably without tumor formation.  These redirected breast cancer cells exhibited no evidence of cell-cell fusion, indicating that the ‘normal’ tissue microenvironment exerts dominant control over cancer cell fate.

Recent Publications

A Representative Clinical Course of Progression, with Molecular Insights, of Hormone Receptor-Positive, HER2-Negative Bone Metastatic Breast Cancer

Stromal-derived extracellular vesicles suppress proliferation of bone metastatic cancer cells mediated by ERK2

Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts

Extracellular Vesicles and Bone-Associated Cancer

Combined targeting of PARG and wee1 causes decreased cell survival and DNA damage in an S-phase–dependent manner

Printing the pathway forward in bone metastatic cancer research: Applications of 3d engineered models and bioprinted scaffolds to recapitulate the bone–tumor niche

‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone‐Tumor Mimetic Microenvironment

Novel Techniques to Study the Bone-Tumor Microenvironment

The bone extracellular matrix as an ideal milieu for cancer cell metastases

Osteoblasts are "educated" by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

Cancer metastases to bone: Concepts, mechanisms, and interactions with bone osteoblasts

Understanding mitochondrial polymorphisms in cancer

Mesenchymal Stem Cell Transition to Tumor-Associated Stromal Cells Contributes to Cancer Progression

The Clock Is Ticking: Countdown to Metastases

Tumor-associated stromal cells as key contributors to the tumor microenvironment

Mesenchymal stem/stromal cell-targeted therapies for solid tumors and hematological malignancies

Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

The influence of metastatic breast cancer on the bone microenvironment

The mammary gland microenvironment directs progenitor cell fate in vivo

Osteoblasts are a major source of inflammatory cytokines in the tumor microenvironment of bone metastatic breast cancer

Immortalized, premalignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA

Reprogramming human cancer cells in the mouse mammary gland

Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur, a target area for metastatic breast cancer cell colonization

Ex-vivo analysis of the bone microenvironment in bone metastatic breast cancer

The bone microenvironment in metastasis; what is special about bone?