Secreted factors from metastatic prostate cancer cells stimulate mesenchymal stem cell transition to a pro-tumourigenic ‘activated’ state that enhances prostate cancer cell migration

AbstractBone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.

Download Full-text

Roles of the Na+/H+ Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion

International Journal of Molecular Sciences ◽

10.3390/ijms222413263 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13263

Author(s):

Xiuju Li ◽

Benjamin Buckley ◽

Konstantin Stoletov ◽

Yang Jing ◽

Marie Ranson ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Colony Formation ◽

Prostate Cancer Cell ◽

Cancer Cell Migration ◽

Prostate Cancer Cells

Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis. Here, we examine the role of the Na+/H+ exchanger isoform 1 (NHE1) and uPA in DU 145 prostate cancer cell migration and colony formation. Knockout of NHE1 reduced cell migration. The effects of a series of novel NHE1/uPA hexamethylene-amiloride-based inhibitors with varying efficacy towards NHE1 and uPA were examined on prostate cancer cells. Inhibition of NHE1—alone, or with inhibitors combining NHE1 or uPA inhibition—generally did not prevent prostate cancer cell migration. However, uPA inhibition—but not NHE1 inhibition—prevented anchorage-dependent colony formation. Application of inhibitors at concentrations that only saturate uPA inhibition decreased tumor invasion in vivo. The results suggest that while knockout of NHE1 affects cell migration, these effects are not due to NHE1-dependent proton translocation. Additionally, while neither NHE1 nor uPA activity was critical in cell migration, only uPA activity appeared to be critical in anchorage-dependent colony formation of DU 145 prostate cancer cells and invasion in vivo.

Download Full-text

Monensin Induced Oxidative Stress Reduces Prostate Cancer Cell Migration and Cancer Stem Cell Population

Oxidative Stress and Diseases ◽

10.5772/34713 ◽

2012 ◽

Cited By ~ 1

Author(s):

Kirsi Ketola ◽

Anu Vuoristo ◽

Matej Orei ◽

Olli Kallioniemi ◽

Kristiina Ilji

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Stem Cell ◽

Cell Migration ◽

Cancer Stem Cell ◽

Cancer Cell ◽

Cell Population ◽

Prostate Cancer Cell ◽

Stem Cell Population ◽

Cancer Cell Migration

Download Full-text

Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells

Journal of Clinical Medicine ◽

10.3390/jcm8030354 ◽

2019 ◽

Vol 8 (3) ◽

pp. 354 ◽

Cited By ~ 6

Author(s):

Kouji Izumi ◽

Atsushi Mizokami

Keyword(s):

Prostate Cancer ◽

Cell Migration ◽

Androgen Receptor ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Metastasis ◽

Prostate Cancer Cell ◽

Standard Form ◽

Cancer Cell Migration ◽

Prostate Cancer Cells

Androgen/androgen receptor (AR) signaling is a significant driver of prostate cancer progression, therefore androgen-deprivation therapy (ADT) is often used as a standard form of treatment for advanced and metastatic prostate cancer patients. However, after several years of ADT, prostate cancer progresses to castration-resistant prostate cancer (CRPC). Androgen/AR signaling is still considered an important factor for prostate cancer cell survival following CRPC progression, while recent studies have reported dichotomic roles for androgen/AR signaling. Androgen/AR signaling increases prostate cancer cell proliferation, while simultaneously inhibiting migration. As a result, ADT can induce prostate cancer metastasis. Several C-C motif ligand (CCL)-receptor (CCR) axes are involved in cancer cell migration related to blockade of androgen/AR signaling. The CCL2-CCR2 axis is negatively regulated by androgen/AR signaling, with the CCL22-CCR4 axis acting as a further downstream mediator, both of which promote prostate cancer cell migration. Furthermore, the CCL5-CCR5 axis inhibits androgen/AR signaling as an upstream mediator. CCL4 is involved in prostate carcinogenesis through macrophage AR signaling, while the CCL21-CCR7 axis in prostate cancer cells is activated by tumor necrotic factor, which is secreted when androgen/AR signaling is inhibited. Finally, the CCL2-CCR2 axis has recently been demonstrated to be a key contributor to cabazitaxel resistance in CRPC.

Download Full-text