Skip to main content
Top
Published in: Clinical & Experimental Metastasis 3/2010

01-03-2010 | Research Paper

In vitro metastatic colonization of human ovarian cancer cells to the omentum

Authors: Shaheena M. Khan, Holly M. Funk, Sophie Thiolloy, Tamara L. Lotan, Jonathan Hickson, Gail S. Prins, Angela F. Drew, Carrie W. Rinker-Schaeffer

Published in: Clinical & Experimental Metastasis | Issue 3/2010

Login to get access

Abstract

Despite the potentially crucial contributions of the omentum in the regulation of ovarian cancer metastatic growth, it remains a poorly understood organ. Due to its anatomic location and structural fragility, the omentum presents inherent challenges to mechanism-based in vivo studies. Thus, the availability of an ex vivo omental model would, in part, address some of these difficulties posed. Here we describe a technique for identifying, isolating and maintaining ex vivo cultures of omenta from immune-compromised and -competent mice. Ex vivo culture conditions were developed that maintain tissue viability, architecture, and function for up to 10 days. Further experiments demonstrate that the ex vivo culture conditions allow for the proliferation of ovarian cancer cells in vitro and support a similar pattern of microscopic lesions after either intraperitoneal injection of ovarian cancer cells or co-culture of ovarian cancer cells with the omentum. In agreement with previous studies from our laboratory, histologic evaluation of these specimens found that ovarian cancer cells, as well as other peritoneal cancer cells, preferentially accumulate in, and colonize, omental areas rich in immune cells. We now recognize that these are specific, functional structures referred to as milky spots. In sum, these are foundational studies of a readily accessible model, which is easily manipulated and can be immediately used to study the dynamic process of omental colonization. It is hoped that investigators will use the data herein as a starting point for refinements and modifications which will enable them to tailor the model to the specific needs of the experimental question(s) they wish to pursue.
Literature
1.
2.
go back to reference Ozols RF, Bookman MA, Connolly DC et al (2004) Focus on epithelial ovarian cancer. Cancer Cell 5(1):19–24CrossRefPubMed Ozols RF, Bookman MA, Connolly DC et al (2004) Focus on epithelial ovarian cancer. Cancer Cell 5(1):19–24CrossRefPubMed
3.
go back to reference Covens AL (2000) A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol 78:269–274 Covens AL (2000) A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol 78:269–274
4.
go back to reference Bristow RE, Puri I, Chi DS (2009) Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 112(1):265–274CrossRefPubMed Bristow RE, Puri I, Chi DS (2009) Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 112(1):265–274CrossRefPubMed
5.
go back to reference Bristow RE, Chi DS (2006) Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol 103(3):1070–1076CrossRefPubMed Bristow RE, Chi DS (2006) Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol 103(3):1070–1076CrossRefPubMed
6.
go back to reference Smith SC, Theodorescu D (2009) Learning therapeutic lessons from metastasis suppressor proteins. Nat Rev Cancer 9(4):253–264CrossRefPubMed Smith SC, Theodorescu D (2009) Learning therapeutic lessons from metastasis suppressor proteins. Nat Rev Cancer 9(4):253–264CrossRefPubMed
7.
go back to reference Bodenstine TM, Welch DR (2008) Metastasis suppressors and the tumor microenvironment. Cancer Microenviron 1(1):1–11CrossRefPubMed Bodenstine TM, Welch DR (2008) Metastasis suppressors and the tumor microenvironment. Cancer Microenviron 1(1):1–11CrossRefPubMed
8.
go back to reference Schwartz PE (1981) Surgical management of ovarian cancer. Arch Surg 116(1):99–106PubMed Schwartz PE (1981) Surgical management of ovarian cancer. Arch Surg 116(1):99–106PubMed
9.
go back to reference Buy JN, Moss AA, Ghossain MA et al (1988) Peritoneal implants from ovarian tumors: CT findings. Radiology 169(3):691–694PubMed Buy JN, Moss AA, Ghossain MA et al (1988) Peritoneal implants from ovarian tumors: CT findings. Radiology 169(3):691–694PubMed
10.
go back to reference Wilkosz S, Ireland G, Khwaja N et al (2005) A comparative study of the structure of human and murine greater omentum. Anat Embryol (Berl) 209(3):251–261CrossRef Wilkosz S, Ireland G, Khwaja N et al (2005) A comparative study of the structure of human and murine greater omentum. Anat Embryol (Berl) 209(3):251–261CrossRef
11.
go back to reference Simer PH (1948) The drainage of particulate matter from the peritoneal cavity into the lymph vessels of the diaphragm. Anat Rec 101(3):333–351CrossRefPubMed Simer PH (1948) The drainage of particulate matter from the peritoneal cavity into the lymph vessels of the diaphragm. Anat Rec 101(3):333–351CrossRefPubMed
12.
go back to reference Pond CM (2005) Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 73(1):17–30CrossRefPubMed Pond CM (2005) Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 73(1):17–30CrossRefPubMed
13.
go back to reference Liebermann-Meffert D (2000) The greater omentum. Anatomy, embryology, and surgical applications. Surg Clin North Am 80(1):275–293 (xii) Liebermann-Meffert D (2000) The greater omentum. Anatomy, embryology, and surgical applications. Surg Clin North Am 80(1):275–293 (xii)
14.
go back to reference Gerber SA, Rybalko VY, Bigelow CE et al (2006) Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am J Pathol 169(5):1739–1752CrossRefPubMed Gerber SA, Rybalko VY, Bigelow CE et al (2006) Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am J Pathol 169(5):1739–1752CrossRefPubMed
15.
go back to reference Kenny HA, Krausz T, Yamada SD et al (2007) Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. Int J Cancer 121(7):1463–1472CrossRefPubMed Kenny HA, Krausz T, Yamada SD et al (2007) Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. Int J Cancer 121(7):1463–1472CrossRefPubMed
16.
go back to reference Zhang XY, Pettengell R, Nasiri N et al (1999) Characteristics and growth patterns of human peritoneal mesothelial cells: comparison between advanced epithelial ovarian cancer and non-ovarian cancer sources. J Soc Gynecol Investig 6(6):333–340CrossRefPubMed Zhang XY, Pettengell R, Nasiri N et al (1999) Characteristics and growth patterns of human peritoneal mesothelial cells: comparison between advanced epithelial ovarian cancer and non-ovarian cancer sources. J Soc Gynecol Investig 6(6):333–340CrossRefPubMed
17.
go back to reference Stylianou E, Jenner LA, Davies M et al (1990) Isolation, culture and characterization of human peritoneal mesothelial cells. Kidney Int 37(6):1563–1570CrossRefPubMed Stylianou E, Jenner LA, Davies M et al (1990) Isolation, culture and characterization of human peritoneal mesothelial cells. Kidney Int 37(6):1563–1570CrossRefPubMed
18.
go back to reference Nakanishi M, Hamazaki TS, Komazaki S et al (2007) Pancreatic tissue formation from murine embryonic stem cells in vitro. Differentiation 75(1):1–11CrossRefPubMed Nakanishi M, Hamazaki TS, Komazaki S et al (2007) Pancreatic tissue formation from murine embryonic stem cells in vitro. Differentiation 75(1):1–11CrossRefPubMed
19.
go back to reference Nakamura M, Katabuchi H, Ohba T et al (1994) Isolation, growth and characteristics of human ovarian surface epithelium. Virchows Arch 424(1):59–67CrossRefPubMed Nakamura M, Katabuchi H, Ohba T et al (1994) Isolation, growth and characteristics of human ovarian surface epithelium. Virchows Arch 424(1):59–67CrossRefPubMed
20.
go back to reference Murray H (1994) Human omental mesothelial cells: a simple method for isolation and discrimination from endothelial cells. In Vitro Cell Dev Biol 30:145–147CrossRef Murray H (1994) Human omental mesothelial cells: a simple method for isolation and discrimination from endothelial cells. In Vitro Cell Dev Biol 30:145–147CrossRef
21.
go back to reference Lai KN, Ho SK, Leung J et al (2001) Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid. Cell Biol Int 25(5):445–450CrossRefPubMed Lai KN, Ho SK, Leung J et al (2001) Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid. Cell Biol Int 25(5):445–450CrossRefPubMed
22.
go back to reference Hjelle JT, Golinska BT, Waters DC et al (1989) Isolation and propagation in vitro of peritoneal mesothelial cells. Perit Dial Int 9(4):341–347PubMed Hjelle JT, Golinska BT, Waters DC et al (1989) Isolation and propagation in vitro of peritoneal mesothelial cells. Perit Dial Int 9(4):341–347PubMed
23.
go back to reference Fedorko ME, Hirsch JG, Fried B (1971) Studies on transport of macromolecules and small particles across mesothelial cells of the mouse omentum. II. Kinetic features and metabolic requirements. Exp Cell Res 69(2):313–323 Fedorko ME, Hirsch JG, Fried B (1971) Studies on transport of macromolecules and small particles across mesothelial cells of the mouse omentum. II. Kinetic features and metabolic requirements. Exp Cell Res 69(2):313–323
24.
go back to reference Bot J, Whitaker D, Vivian J et al (2003) Culturing mouse peritoneal mesothelial cells. Pathol Res Pract 199(5):341–344CrossRefPubMed Bot J, Whitaker D, Vivian J et al (2003) Culturing mouse peritoneal mesothelial cells. Pathol Res Pract 199(5):341–344CrossRefPubMed
25.
go back to reference Hickson JA, Huo D, Vander Griend DJ et al (2006) The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma. Cancer Res 66(4):2264–2270CrossRefPubMed Hickson JA, Huo D, Vander Griend DJ et al (2006) The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma. Cancer Res 66(4):2264–2270CrossRefPubMed
26.
go back to reference Delves PJ, Martin, SJ, Burton DR, Roitt IM (2006) Roitt’s essential immunology. Blackwell, Malden Delves PJ, Martin, SJ, Burton DR, Roitt IM (2006) Roitt’s essential immunology. Blackwell, Malden
27.
go back to reference Lotan T, Hickson J, Souris J, et al. (2008) c-Jun NH2-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4-mediated inhibition of SKOV3ip.1 ovarian cancer metastasis involves growth arrest and p21 up-regulation. Cancer Res 68(7):2166–2175 Lotan T, Hickson J, Souris J, et al. (2008) c-Jun NH2-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4-mediated inhibition of SKOV3ip.1 ovarian cancer metastasis involves growth arrest and p21 up-regulation. Cancer Res 68(7):2166–2175
28.
go back to reference Ranvier H (1874) Du developpement t de l’accroissement des vaisseaux sanguins. Arch Physiol 1:429 Ranvier H (1874) Du developpement t de l’accroissement des vaisseaux sanguins. Arch Physiol 1:429
29.
go back to reference Strobel T, Swanson L, Cannistra SA (1997) In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. Cancer Res 57(7):1228–1232PubMed Strobel T, Swanson L, Cannistra SA (1997) In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. Cancer Res 57(7):1228–1232PubMed
30.
go back to reference Rieppi M, Vergani V, Gatto C et al (1999) Mesothelial cells induce the motility of human ovarian carcinoma cells. Int J Cancer 80(2):303–307CrossRefPubMed Rieppi M, Vergani V, Gatto C et al (1999) Mesothelial cells induce the motility of human ovarian carcinoma cells. Int J Cancer 80(2):303–307CrossRefPubMed
31.
go back to reference Ahmed N, Oliva K, Wang Y et al (2003) Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta1 integrin complex in colon cancer cells. Br J Cancer 89(2):374–384CrossRefPubMed Ahmed N, Oliva K, Wang Y et al (2003) Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta1 integrin complex in colon cancer cells. Br J Cancer 89(2):374–384CrossRefPubMed
32.
go back to reference Recklinghausen FTv (1863) Uber Eiter und Bindegewebskorperchen. Virchow’s Arch 28:157–197 Recklinghausen FTv (1863) Uber Eiter und Bindegewebskorperchen. Virchow’s Arch 28:157–197
33.
go back to reference Recklinghausen FTv (1863) Zur Fettresorption. Virchow’s Arch 26:172–208 Recklinghausen FTv (1863) Zur Fettresorption. Virchow’s Arch 26:172–208
34.
go back to reference Mironov VA, Gusev SA, Baradi AF (1979) Mesothelial stomata overlying omental milky spots: scanning electron microscopic study. Cell Tissue Res 201(2):327–330CrossRefPubMed Mironov VA, Gusev SA, Baradi AF (1979) Mesothelial stomata overlying omental milky spots: scanning electron microscopic study. Cell Tissue Res 201(2):327–330CrossRefPubMed
35.
go back to reference Sorensen EW, Gerber SA, Sedlacek AL et al. (2009) Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res 45(2–3):185–194CrossRef Sorensen EW, Gerber SA, Sedlacek AL et al. (2009) Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res 45(2–3):185–194CrossRef
Metadata
Title
In vitro metastatic colonization of human ovarian cancer cells to the omentum
Authors
Shaheena M. Khan
Holly M. Funk
Sophie Thiolloy
Tamara L. Lotan
Jonathan Hickson
Gail S. Prins
Angela F. Drew
Carrie W. Rinker-Schaeffer
Publication date
01-03-2010
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 3/2010
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-010-9317-0

Other articles of this Issue 3/2010

Clinical & Experimental Metastasis 3/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine