Soft fibrin gels promote selection and growth of tumorigenic cells

Abstract

The identification of stem-cell-like cancer cells through conventional methods that depend on stem-cell markers is often unreliable. We developed a mechanical method of selecting tumourigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem-cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe-combined-immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as 10 such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

“…17 These TRCs were generated by the previously reported soft 3D fibrin gel method. 5 About 1,250 tumor cells were mixed with 125 mL fibrinogen solution (2 mg/mL fibrinogen, activated by 0.5 units of thrombin) and seeded on 24-well plate. Adapting this method, we found that combination of Cis-MPs and LDI more effectively disrupted different types of TRCs (H22, CT26 and Lewis) ( Fig.…”

“…Detailed methods are described as previously. 5 Tumor cells were detached from the standard culture conditions and suspended in culture medium (10% FBS) and cell density was adjusted to 10 4 cells/mL. Fibrinogen was diluted into 2 mg/mL with T7 buffer (pH 7.4, 50 mM Tris, 150 mM NaCl).…”

“…[1][2][3][4] Stem cell-like cancer cells that can repopulate tumors tumor-repopulating cells (TRC) [5][6][7] are a self-renewing, highly tumorigenic subpopulation of cancer cells and play crucial roles in the initiation, promotion and progression of tumorigenesis. Recent studies have highlighted the critical role of TRCs in regulating the effect of immune cells on tumors.…”

Oncogenes and the coagulation system – forces that modulate dormant and aggressive states in cancer

“…In this regard, Karpatkin first postulated that thrombin may trigger growth of dormant cancer cells [104], a notion of considerable importance given microscopic prevalence of ostensibly transformed cells in the adult and elderly population [105]. Contact with soft fibrin has also been proposed as a milieu that may enrich for CSCs [106].…”

Biomimetic Model of Tumor Microenvironment on Microfluidic Platform

“…[25,26] Our results sup port a previous report that a soft fibrin gel promoted the for mation of tumorigenic stem cell like colonies. [27] Although we observed increased proliferation and filopodial projection in the collagen fibrin composite matrix, rigidity alone is insufficient to explain the amplified fibroblast coculture effect with the collagen fibrin mixture. Another important factor that regulates cancer physiology in the TME is integrin receptor signaling of the cancer cells.…”