Modulation of prostate cancer growth in bone microenvironments

Abstract

Bone remains one of the major sites, and most lethal host organs, for prostate cancer metastasis. Prostate cell spread and establishment in bone depends on multiple reciprocal modifications of bone stromal and epithelial cancer cell behaviors. This review focuses on recent advances in the characterization of cell-cell and cell-matrix interplay, effects on cell growth, adhesion and invasion, and several therapeutic possibilities for co-targeting prostate cancer cells and bone stroma. We address the topic from three main perspectives: (1) the normal and aging bone stromal environment, (2) the "reactive" bone stromal environment, and (3) the cancerous prostate epithelial cells themselves. First, normal, and especially aging, bones provide uniquely rich and "fertile soil" for roaming cancer cells. The interactions between prostate cancer cells and insoluble extracellular matrices, soluble growth factors, and/or sex steroid hormones trigger bone remodeling, through increased osteoclastogenesis and furthur matrix metalloproteinase activity. Second, after cancer cell arrival and establishment in the bone, host stromal cells respond, becoming "reactive" in a process again involving extracellular matrix remodeling, together with growth factor and steroid receptor signaling this process ultimately enhances cancer cell migration, stromal transdifferentiation, and invasion of the cancer tissues by stromal, inflammatory, and immune-responsive cells. Third, prostate cancer cells also respond to supportive bone microenvironments, where soluble and matrix-associated molecules affect cancer cell growth and gene expression, especially altering cancer cell surface receptor and integrin-mediated cell signaling. We discuss both integrin cell-matrix and gap junctional cell-cell communication between cancer cells and their microenvironments during prostate cancer progression.

Modeling the Prostate Stem Cell Niche: An Evaluation of Stem Cell Survival and Expansion In Vitro

“…Bone marrow stroma, and stroma derived from prostate cancer both can stimulate prostate cancer growth [16,17]; therefore, they represent potential candidates for stimulating normal stem cell growth. Using 3 different patient aggregates of primary CD133…”

Tumor proliferation and diffusion on percolation clusters

“…Figure 5b shows the evolution of the tumor peak location with an emerging and leaping characteristic over time t. Take the peak p 9 for example. It appears at t = 71 and remains unchanged until t = 210, which we considered to be a quasi-steady state for the peak p 9 . Another new peak p 10 emerges at t = 211 as evolved from the previous peak p 9 .…”

“…A very important feature of tumor metastases is the ability of different tumor types to metastasize frequently to a similar range of organ sites [6][7][8] and different types of tumors have different ranges of target tissues. For example, the metastasis of prostate cancer is largely confined to bone [9] while that of ocular melanoma is almost exclusively limited to the liver [3]. Adenocarcinomas of the breast and lung typically relapse within the bone, lung, liver, and brain [8].…”

Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

“…Use of an orthotopic model is essential in prostate cancer because of tumor-stromal interactions (28,29), which are particularly important to consider when treatments in combination with AD are being evaluated. This is the first in vivo investigation of the effects of AS-MDM2 on response to AD.…”